title: Epidermal Growth Factor Tethered to β-Tricalcium Phosphate Bone Scaffolds via a High-Affinity Binding Peptide Enhances Survival of Human Mesenchymal Stem Cells/Multipotent Stromal Cells in an Immune-Competent Parafascial Implantation Assay in Mice.
abstract: : Mesenchymal stem cells/multipotent stromal cells (MSCs) are attractive candidates for cell therapies owing to their ability to differentiate into many lineages. However, these cells often fail to survive when implanted into a harsh wound environment, limiting efficacy in vivo. To improve MSC survival, we previously found that tethered epidermal growth factor (tEGF) molecules that restrict epidermal growth factor receptor (EGFR) signaling to the cell surface provide resistance to death signals. To adapt this system to wound healing, we tethered epidermal growth factor (EGF) to tricalcium phosphate (TCP) particle scaffolds, clinically used in bone healing. Human primary MSCs seeded on TCP and mixed into a collagen-based gel were injected in the perifascial space of immunocompetent mice with or without tEGF attached to the surface. We found that tethering EGF to the TCP scaffolds yielded approximately a fourfold increase in MSC survival compared with non-EGF scaffolds at 21 days, as well as significant improvements in survival in the short term at 2 and 7 days after implantation. Overall, our approach to sustaining EGFR signaling reduced MSC death in vivo and may be useful for future cell therapies where MSCs typically die on implantation.
  
  
  CONCLUSIONS
  Stem cells are limited as tissue replacements owing to rapid death induced in the hostile wound environment. It has been found that restricting epidermal growth factor (EGF) receptor signaling to the membrane provides a survival advantage. This report elucidates a method to tether EGF to bone induction material to improve the survival of mesenchymal stem cells/multipotent stromal cells in vivo.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Nuschke
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Rodrigues
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Department of Health Promotion and Development, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|VA Pittsburgh Health System, Pittsburgh, Pennsylvania, USA.
authors.forename: Cecelia
authors.initials: C
authors.lastname: Yates
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Whaley
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Stolz
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Griffith
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA wellsa@upmc.edu.|McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|VA Pittsburgh Health System, Pittsburgh, Pennsylvania, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Wells
keywords: Mesenchymal stem cells; Multipotent stem cells; Stem cell survival; Surface-tethered epidermal growth factor; β-Tricalcium phosphate