Tethered EGF Provides a Survival Advantage to Mesenchymal Stem Cells

¹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Harvard School of Dental Medicine, Boston, Massachusetts
² Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
³ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
⁴ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
⁵ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts

^* To whom correspondence should be addressed. E-mail: Griff{at}mit.edu.

	Abstract

Mesenchymal stem cells (MSC) can act as a pluripotent source of reparative cells during injury and therefore have great potential in regenerative medicine and tissue engineering. However, the response of MSC to many growth factors and cytokines is unknown. Many envisioned applications of MSC, such as treating large defects in bone, involve in vivo implantation of MSC attached to a scaffold, a process that creates an acute inflammatory environment that may be hostile to MSC survival. Here, we investigate cellular responses of MSC on a biomaterial surface covalently modified with epidermal growth factor (EGF). We find that surface-tethered EGF promotes both cell spreading and survival more strongly than saturating concentrations of soluble EGF. By sustaining MEK-ERK signaling, tethered EGF increases the contact of MSC with an otherwise moderately adhesive synthetic polymer and confers resistance to cell death induced by the proinflammatory cytokine, FasL. We conclude that tethered EGF may offer a protective advantage to MSC in vivo during acute inflammatory reactions to tissue engineering scaffolds. The tethered EGF-modified polymers described here could be used together with structural materials to construct MSC scaffolds for the treatment of hard-tissue lesions, such as large bony defects.

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