title: Control of neural cell composition in poly(ethylene glycol) hydrogel culture with soluble factors.
abstract: Poly(ethylene glycol) (PEG) hydrogels are being developed as cell delivery vehicles that have great potential to improve neuronal replacement therapies. Current research priorities include (1) characterizing neural cell growth within PEG hydrogels relative to standard culture systems and (2) generating neuronal-enriched populations within the PEG hydrogel environment. This study compares the percentage of neural precursor cells (NPCs), neurons, and glia present when dissociated neural cells are seeded within PEG hydrogels relative to standard monolayer culture. Results demonstrate that PEG hydrogels enriched the initial cell population for NPCs, which subsequently gave rise to neurons, then to glia. Relative to monolayer culture, PEG hydrogels maintained an increased percentage of NPCs and a decreased percentage of glia. This neurogenic advantage of PEG hydrogels is accentuated in the presence of basic fibroblast growth factor and epidermal growth factor, which more potently increase NPC and neuronal expression markers when applied to cells cultured within PEG hydrogels. Finally, this work demonstrates that glial differentiation can be selectively eliminated upon supplementation with a γ-secretase inhibitor. Together, this study furthers our understanding of how the PEG hydrogel environment influences neural cell composition and also describes select soluble factors that are useful in generating neuronal-enriched populations within the PEG hydrogel environment.
authors.affiliation: Department of Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Mooney
authors.forename: Sarah
authors.initials: S
authors.lastname: Haeger
authors.forename: Rasheed
authors.initials: R
authors.lastname: Lawal
authors.forename: Mariah
authors.initials: M
authors.lastname: Mason
authors.forename: Neha
authors.initials: N
authors.lastname: Shrestha
authors.forename: Alexander
authors.initials: A
authors.lastname: Laperle
authors.forename: Kimberly
authors.initials: K
authors.lastname: Bjugstad
authors.forename: Melissa
authors.initials: M
authors.lastname: Mahoney
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor