Differentiation of adult human stem cells guided by mechano-sensing of matrix elasticity


Florian Rehfeldt, rehfeldt@sas.upenn.edu1, Adam J Engler, aengler@seas.upenn.edu2, and Dennis E. Discher1. (1) Chem & Biomol Eng; Cell & Mol Biology and Physics Grad Groups, University of Pennsylvania, 129 Towne Building, 220 South 33rd Street, Philadelphia, PA 19104-6315, (2) Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 112 Towne Building, 220 South 33rd Street, Philadelphia, PA 19104-6391
Human mesenchymal stem cells (MSCs) from bone marrow are promising candidates for potential therapeutic applications since they can differentiate into various lineages. State of the art differentiation of these pluripotent cells is done biochemically using appropriate growth factors. But biochemical stimuli are just one part of the complex chemo-physical environment cells face in vivo. It is now well acknowledged that cells feel and respond to their physical environment and that these physical cues are as important as the biochemical ones. Recently, we demonstrated that substrate elasticity can even direct MSC differentiation to osteogenic, myogenic or neurogenic cells. While these experimental results are striking, understanding of the complex underlying molecular mechanisms of force sensing and transduction is only at its very beginning. A detailed insight to cell adhesion on tunable biomimetic substrates is given and the connection between cell adhesion, mechanical properties of the substrate and stem cell differentiation is highlighted.