title: Neurotropic growth factors and glycosaminoglycan based matrices to induce dopaminergic tissue formation.
abstract: Current cell replacement therapies in Parkinson's disease (PD) are limited by low survival of transplanted cell and lacking regeneration of neuronal circuitries. Therefore, bioartificial cell carriers and growth/differentiation factors are applied to improve the integration of transplants and maximize newly generated and/or residual dopaminergic function. In this work, biohybrid poly(ethylene glycol) (starPEG)-heparin hydrogels releasing fibroblast growth factor 2 (FGF-2) and glial-derived neurotrophic factor (GDNF) were used to trigger dopaminergic tissue formation by primary murine midbrain cells in vitro. Matrix-delivered FGF-2 enhanced cell viability while release of GDNF had a pro-neuronal/dopaminergic effect. Combined delivery of both factors from the glycosaminoglycan-based matrices resulted in a tremendous improvement in survival and maturation capacity of dopaminergic neurons as obvious from tyrosine hydroxylase expression and neurite outgrowth. The reported data demonstrate that glycosaminoglycan-based hydrogels can facilitate the administration of neurotrophic factors and are therefore instrumental in potential future treatments of PD.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307 Dresden, Germany; Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Schurig
authors.affiliation: Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany; Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), 01069 Dresden, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zieris
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307 Dresden, Germany; Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hermann
authors.affiliation: Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany; Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), 01069 Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Freudenberg
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Heidel
authors.affiliation: Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany; Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), 01069 Dresden, Germany.
authors.forename: Milauscha
authors.initials: M
authors.lastname: Grimmer
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307 Dresden, Germany; Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.affiliation: Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany; Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), 01069 Dresden, Germany. Electronic address: werner@ipfdd.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000187:drug effects; D065546:Drug Liberation; D005260:Female; D005333:Fetus / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry; D020100:Hydrogels / Q000138:chemical synthesis; D008636:Mesencephalon / Q000166:cytology; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D011092:Polyethylene Glycols / Q000138:chemical synthesis; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D006025:Glycosaminoglycans; D020100:Hydrogels; D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; D006493:Heparin
keywords: Cell replacement; Glycosaminoglycan; Hydrogel; Neural stem cells; Neurotrophic growth factor