Immobilized Epidermal Growth Factor Promotes Stem Cell Growth and Differentiation

Human EGF is a 6,045 Da protein with 53 amino acid residues and three intramolecular disulfide bonds. EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface and stimulating the intrinsic protein-tyrosine kinase activity of the receptor. The tyrosine kinase activity in turn initiates a signal transduction cascade which results in a variety of biochemical changes within the cell--a rise in intracellular calcium levels, increased glycolysis and protein synthesis, and increases in the expression of certain genes including the gene for EGFR--that ultimately lead to DNA synthesis and cell proliferation. The cell eventually denatures the EGF.
In the current study, investigators at the Massachusetts Institute of Technology (MIT; Boston, USA) immobilized EGF on a polymer surface (scaffold) before allowing it to interact with an MSC culture. They reported in the January 18, 2007, online edition of Stem Cells that immobilized EGF promoted both cell spreading and survival more strongly than saturating concentrations of soluble EGF. Immobilized EGF increased the contact of MSC with an otherwise moderately adhesive synthetic polymer and conferred resistance to cell death induced by the proinflammatory cytokine, FasL.
"Putting EGF and MSC on a scaffold is appealing because then you can control the concentration and location and so forth,” said senior author Dr. Linda Griffith, professor of biological engineering at the Massachusetts Institute of Technology. "The ceramic and polymer scaffold, which remains in the patient's body during healing but then resorbs, also provides structure for the stem cells as they grow into new bone cells.
"We found that when EGF was tethered to the surface it elicited different cell responses than it did when given to cells in the usual soluble form,” said Dr. Griffith. "When tethered, it protected the cells from being killed by pro-death inflammatory signals. The soluble version of the factor did not protect cells. I am very optimistic about the potential for adult stem cells to be useful clinically for the problems I work on, since there are already some clinical successes based on these cells. Continuing, careful, methodical work will lead to improved therapies based on adult stem cells. We are aiming to expand the range of therapies that work in the clinic.”


Related Links:
Massachusetts Institute of Technology