Tethered Epidermal Growth Factor Provides a Survival Advantage to Mesenchymal Stem Cells

Abstract

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 investigated cellular responses of MSC on a biomaterial surface covalently modified with epidermal growth factor (EGF). We found that surfacetethered EGF promotes both cell spreading and survival more strongly than saturating concentrations of soluble EGF. By sustaining mitogen-activated protein kinase kinase-extracellular-regulated kinase 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, Fas ligand. We concluded 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.

The Lamina Propria of Adult Human Oral Mucosa Harbors a Novel Stem Cell Population

“…hOMSC produce and secrete FGF-2, EGF, VEGF, and NGF. These growth factors, particularly FGF-2 [51][52][53], are known to support cell proliferation. Thus, their activity may explain the high-renewal capacity of hOMSC.…”

Escherichia coli expression and refolding of E/K-coil-tagged EGF generates fully bioactive EGF for diverse applications

“…lated surface through the binding of a His tag fused to the EGF Cterminus and used this system for the expansion of neural stem cells. In addition, tethering of EGF to a polymer substrate has been shown to improve the proliferation and survival of mesenchymal stem cells [39], and it has been demonstrated that immobilized EGF gradient surfaces induce accelerated and polarized migration of keratinocytes and therefore speed up the wound closure [40].…”

Endothelial cells guided by immobilized gradients of vascular endothelial growth factor on porous collagen scaffolds

“…Immobilization of biomolecular cues, such as growth factors onto tissue engineering scaffolds, has been investigated in several studies [44,45]. Immobilized growth factors provide localized and prolonged cell stimulation because their rate of internalization is reduced and they have a longer half-life [46,47]. Pro-angiogenic growth factors have been immobilized on biomaterials to enhance vascularization within the construct.…”