Results 1 to 3 of 3

Thread: Chemical Turns Stem Cells Into Neurons Say Scientists At Scripps Research Institute/Molecules Turn Stem Cells into Brain Cells

  1. #1
    Senior Member Max's Avatar
    Join Date
    Jul 2001
    Location
    Montreal,Province of Quebec, CANADA
    Posts
    15,036

    Chemical Turns Stem Cells Into Neurons Say Scientists At Scripps Research Institute/Molecules Turn Stem Cells into Brain Cells

    Chemical Turns Stem Cells Into Neurons Say Scientists At Scripps Research Institute
    A group of researchers from The Scripps Research Institute (TSRI) and the Genomics Institute of the Novartis Research Foundation (GNF) have identified a small chemical molecule that controls the fate of embryonic stem cells. "We found molecules that can direct the embryonic stem cells to [become] neurons," says Sheng Ding, who recently completed his Ph.D. work at TSRI and is becoming an assistant professor in the chemistry department. Ding is the lead author on the study, which is described in an upcoming issue of the journal Proceedings of the National Academy of Sciences.

    "This is an important step in our efforts to understand how to modulate stem cell proliferation and fate," says Peter Schultz, Ph.D., TSRI professor of chemistry and Scripps Family Chair of TSRI's Skaggs Institute for Chemical Biology.

    The Promise of Stem Cell Therapy

    Stem cells have huge potential in medicine because they have the ability to differentiate into many different cell types--potentially providing doctors with the ability to regenerate cells that have been permanently lost by a patient.

    For instance, the damage of neurodegenerative diseases like Parkinson's, in which dopaminergic neurons in the brain are lost, may be ameliorated by regenerating neurons. Another example is Type 1 diabetes, an autoimmune condition in which pancreatic islet cells are destroyed by the body's immune system. Because stem cells have the power to differentiate into islet cells, stem cell therapy could potentially cure this chronic condition.

    However bright this promise, many barriers must be overcome before stem cells can be used in medicine. Scientists have yet to understand the natural signaling mechanisms that control stem cell fate and to develop ways to manipulate these controls.

    "We still have much to learn about how to direct stem cells to specific lineages," says Ding.

    In order to address this problem, Schultz and Ding sought to find small chemical molecules that could permit precise control over the fate of pluripotent mouse embryonic stem cells--which, like human embryonic stem cells, have the ability to differentiate into all cell types.

    The scientists screened some 50,000 small molecules from a combinatorial small molecule library that they synthesized at GNF. Just as a common library is filled with different books, this combinatorial library is filled with different small organic compounds.

    From this assortment, Schultz and Ding designed a method to identify molecules able to differentiate the cells into neurons. They engineered embryonal carcinoma (EC) cells with a reporter gene encoding a protein called luciferase, and they inserted this luciferase gene downstream of the promoter sequence of a gene that is only expressed in neuronal cells. Then they placed these EC cells into separate wells and added different chemicals from the library to each. If the engineered EC cells in any particular well were induced to become neurons, the neurons would express luciferase--which can convert a non-luminescent substrate to a luminescent product. This product makes that well easy to detect from tens of thousands of other wells with GNF's state-of-the-art high-throughput screening equipment.

    Once they found some cells they believed to be neurons by treatment with certain small molecules, the scientists used more rigorous assays to confirm this, including staining the cells for characteristic markers and examining the shape of individual cells under the microscope. Neurons have a characteristic round soma body and asymmetric multiple processes.

    In the end, Schultz and Ding found a number of molecules that were able to induce neuronal differentiation, and they chose one, called TWS119, for further studies.

    When they examined the mechanism of TWS119 in detail, they found that it binds to a cellular kinase enzyme called glycogen synthase kinase-3beta (GSK-3beta). This is a multifunctional "signaling" enzyme involved in a number of physiological signaling processes whereby it modulates other enzymes by attaching a phosphate group to them.

    The fact that modulating GSK-3beta leads the cells to become neurons reveals basic information on the complicated signaling cascade that turns a stem cell into a neuron. And the fact that TWS119 modulates the activity of GSK-3beta suggests that TWS119 is likely to provide new insights into the molecular mechanism that controls stem cell fate, and may ultimately be useful to in vivo stem cell therapy.

    Schultz and Ding are still working on describing the exact mechanism whereby this binding directs the cell to become a neuron.

    ###

    The article, "Synthetic Small Molecules that Control Stem Cell Fate" is authored by Sheng Ding, Tom Y.H. Wu, Achim Brinker, Eric C. Peters, Wooyoung Hur, Nathanael S. Gray, and Peter G. Schultz and will be available online next week at: http://www.pnas.org/cgi/10.1073/pnas.0732087100. The article will also be published in an upcoming issue of the journal Proceedings of the National Academy of Sciences.

    This work was supported by The Skaggs Institute for Research, the Novartis Research Foundation, a Howard Hughes Medical Institute predoctoral fellowship, and a Humboldt Foundation postdoctoral fellowship.

    Editor's Note: The original news release can be found here.


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

    This story has been adapted from a news release issued by Scripps Research Institute.

    http://www.sciencedaily.com/releases...0603082935.htm

    [This message was edited by Max on 06-03-03 at 08:50 PM.]

  2. #2
    Senior Member Max's Avatar
    Join Date
    Jul 2001
    Location
    Montreal,Province of Quebec, CANADA
    Posts
    15,036

    Molecules Turn Stem Cells into Brain Cells

    Molecules Turn Stem Cells into Brain Cells
    Dwayne Hunter
    Betterhumans Staff
    Tuesday, June 03, 2003, 12:43:34 PM CT




    Molecules that modulate embryonic stem cell proliferation and fate have been identified and used to turn stem cells into neurons.

    Researchers from The Scripps Research Institute and the Genomics Institute of the Norvartis Research Foundation describe the discovery in the upcoming issue of the Proceeding of the National Academy of Sciences.

    "We found molecules that can direct embryonic stem cells to become neurons," says Sheng Ding from Scripps, the study's lead author.

    The finding is considered an important step in understanding how to control the production and differentiation of stem cells.

    Signal manipulation

    The ability of stem cells to differentiate into many different cells gives tem huge potential in medicine.

    They can be used for neurodegenerative diseases such as Parkinson's, for example, where the loss of dopaminergic neurons could be ameliorated with neurons from stem cells.

    Stem cells could also help fight type 1 diabetes by differentiating into pancreatic islet cells that have been destroyed by the body's immune system.

    But despite the potential of stem cells, scientists must first understand and develop ways to manipulate the signaling mechanisms that control their fate before they can be used in medicine.

    Screening 50,000 molecules

    Ding and colleagues tried to find small molecules that could permit precise control over the fate of pluripotent mouse embryonic stem cells.

    They screened 50,000 small molecules and designed a method to identify those that could cause stem cells to differentiate into neurons. The method involved using a protein called luciferase to make cells that differentiated into neurons glow.

    Cells believed to be neurons were then analyzed by staining them to highlight characteristic marks and examining them under a microscope.

    Out of many molecules that induced neuronal differentiation, the researchers focused on TWS119, which has the ability to bind a cellular kinase enzyme called glycogen synthase kinase-3beta, a multifunctioning "signaling" enzyme that modulates other enzymes by attaching a phosphate group to them.

    It is the modulation of GSK-3beta by TWSA119 that leads stem cells to become neurons.

    Ding and colleagues are now working to describe the exact mechanism that directs cells to become neurons.
    http://www.betterhumans.com/News/new...D=2003-06-03-2

  3. #3
    Senior Member Max's Avatar
    Join Date
    Jul 2001
    Location
    Montreal,Province of Quebec, CANADA
    Posts
    15,036

    Drug may give cells a fresh start

    Drug may give cells a fresh start
    A chemical could switch adult cells from one type to another.
    30 January 2004
    PHILIP BALL and HELEN PEARSON


    Might we one day regenerate limbs like an salamander?
    © Image Source



    Chemists in California have found a synthetic molecule that seems to reprogramme adult cells to make them more like youthful ones. If the discovery pans out, it could provide an easy source of cells to regenerate tissues damaged by disease or injury.

    Sheng Ding and colleagues of
    http://www.nature.com/nsu/040126/040126-14.html

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •