title: The influence of tethered epidermal growth factor on connective tissue progenitor colony formation.
abstract: Strategies to combine aspirated marrow cells with scaffolds to treat connective tissue defects are gaining increasing clinical attention and use. In situations such as large defects where initial survival and proliferation of transplanted connective tissue progenitors (CTPs) are limiting, therapeutic outcomes might be improved by using the scaffold to deliver growth factors that promote the early stages of cell function in the graft. Signaling by the epidermal growth factor receptor (EGFR) plays a role in cell survival and has been implicated in bone development and homeostasis. Providing epidermal growth factor (EGF) in a scaffold-tethered format may sustain local delivery and shift EGFR signaling to pro-survival modes compared to soluble ligand. We therefore examined the effect of tethered EGF on osteogenic colony formation from human bone marrow aspirates in the context of three different adhesion environments using a total of 39 donors. We found that tethered EGF, but not soluble EGF, increased the numbers of colonies formed regardless of adhesion background, and that tethered EGF did not impair early stages of osteogenic differentiation.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Marcantonio
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Boehm
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rozic
authors.forename: Ada
authors.initials: A
authors.lastname: Au
authors.forename: Alan
authors.initials: A
authors.lastname: Wells
authors.forename: George F
authors.initials: GF
authors.lastname: Muschler
authors.forename: Linda G
authors.initials: LG
authors.lastname: Griffith
mesh_terms: D000327:Adsorption / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003239:Connective Tissue Cells / Q000166:cytology* / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D011108:Polymers; D044967:Serum; D012995:Solubility / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*
chemical_list: D005353:Fibronectins; D010455:Peptides; D011108:Polymers; D004815:Epidermal Growth Factor