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August 23, 2010

Surface that Enables Stem Cell Growth for up to Three Months Developed

The cells at the top are stained to reveal their nuclei, cells in the middle and bottom are stained for proteins linked to pluripotency, Oct4 and SSEA-4. [Ying Mei, Krishanu Saha, Robert Langer, Rudolf Jaenisch, and Daniel G. Anderson]

  • MIT chemical engineers, materials scientists, and biologists have devised a synthetic surface that includes no foreign animal material and allows stem cells to stay alive and continue reproducing for at least three months. It is also reportedly the first synthetic material that allows single cells to form colonies of identical cells, which is necessary to identify cells with desired traits and has been difficult to achieve with existing materials.

    The experiments are detailed in Nature Materials in a paper titled "Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells."

    Scientists who work with human pluripotent stem cells have had trouble growing large enough quantities to perform certain experiments. Furthermore, most materials now used to grow human stem cells include cells or proteins that come from mice embryos, which help stimulate stem cell growth but would likely cause an immune reaction if injected into a human patient. Current growth surfaces, consisting of a plastic dish coated with a layer of gelatin and then a layer of mouse cells or proteins, are notoriously inefficient, according to Krishanu Saha, Ph.D., who works at the Whitehead Institute for Biomedical Research.

    "For therapeutics, you need millions and millions of cells," Dr. Saha adds. "If we can make it easier for the cells to divide and grow, that will really help to get the number of cells you need to do all of the disease studies that people are excited about."

    Previous studies had suggested that several chemical and physical properties of surfaces, including roughness, stiffness, and affinity for water, might play a role in stem cell growth. The researchers created about 500 polymers that varied in those traits, grew stem cells on them, and analyzed each polymer's performance. After correlating surface characteristics with performance, they found that there was an optimal range of surface hydrophobicity, but varying roughness and stiffness did not have much effect on cell growth.

    They also adjusted the composition of the materials including proteins embedded in the polymer. They found that the best polymers contained a high percentage of acrylates, a common ingredient in plastics, and were coated with a protein called vitronectin, which encourages cells to attach to surfaces.

    Using their best-performing material, the researchers got both embryonic and induced pluripotent stem cells to continue growing and dividing for up to three months. They were also able to generate cells in the millions.

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