A combinatorial approach to promoting human embroynic stem cell self-renewal

ORGN 262

Laura L. Kiessling1, Brendan P. Orner, orner@biochem.wisc.edu2, Ratmir Derda, derda@chem.wisc.edu3, Rachel Lewis4, and James Thomson4. (1) Departments of Chemistry and Biochemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, (2) Departments of Biochemistry and Chemistry, University of Wisconsin, Madison, WI 53706, (3) Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706, (4) Department of Anatomy, University of Wisconsin-Madison, Madison, WI
Human embryonic stem cells (ES) hold promise because of their ability to give rise to any human cell type. A significant barrier to the study and use of human cells is the difficulty of maintaining these cells in a pluripotent state. The signals that promote human ES cell self-renewal are different than those required for mouse ES cells; strategies to identify such signals are needed. We envisioned that chemically-defined surfaces and ligands could give rise to large populations of pluripotent human ES cells and specific cell lineages derived from these. Our approach is to elicit the appropriate signals through displays of synthetic and/or naturally-occurring ligands that bind to cell-surface receptors. We have developed a method to screen diverse surfaces to identify those with illuminating cell adhesive or signaling properties. Our approach relies upon self-assembled monolayers (SAMs), which can form surfaces that have been used in cell attachment and patterning studies. The development of a new method to generate SAM arrays and their use in the identification of surfaces that promote human ES cell proliferation will be discussed.