title: Exploration of physical and chemical cues on retinal cell fate.
abstract: Identification of the key components in the physical and chemical milieu directing donor cells into a desired phenotype is a requirement in the investigation of bioscaffolds for the advancement of cell-based therapies for retinal neurodegeneration. We explore the effect of electrospun poly-ε-caprolactone (PCL) fiber scaffold topography and functionalization and culture medium, on the behavior of mouse retinal cells. Dissociated mouse retinal post-natal cells were seeded on random or aligned oriented fibers, with or without laminin coating and cultured with either basic or neurotrophins enriched medium for 7days. Addition of laminin in combination with neurotrophins clearly promoted cell- morphology, fate, and neurite extension. Nanotopography per se significantly affected cell morphology, with mainly bipolar profiles on aligned fibers and more multipolar profiles on random fibers. Laminin induced a remarkable 90° switch of neurite orientation. Herewith, we demonstrate that the chemical cue is stronger than the physical cue for the orientation of retinal neurites and describe the requirement of both neurotrophins and extracellular matrix proteins for extended neurite outgrowth and formation of complex retinal neuronal networks. Therefore, tailor-made PCL fiber mats, which can be physically and chemically modified, indeed influence cell behavior and hence motivate further retinal restorative studies using this system.
authors: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Ophthalmology, Lund, Sweden. Electronic address: marina.castro_zalis@med.lu.se.
authors: Marina Castro
authors: MC
authors: Zalis
authors: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Ophthalmology, Lund, Sweden. Electronic address: atn09sjo@student.lu.se.
authors: Sebastian
authors: S
authors: Johansson
authors: Lund University, Department of Biology, Section of Functional Zoology, Lund, Sweden. Electronic address: per_fredrik.johansson@biol.lu.se.
authors: Fredrik
authors: F
authors: Johansson
authors: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Ophthalmology, Lund, Sweden. Electronic address: ulrica.englund_johansson@med.lu.se.
authors: Ulrica Englund
authors: UE
authors: Johansson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D000071446:Neuronal Outgrowth; D011091:Polyesters / Q000494:pharmacology; D055351:Retinal Neurons / Q000187:drug effects* / Q000648:ultrastructure; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D007797:Laminin; D009414:Nerve Growth Factors; D011091:Polyesters; C016240:polycaprolactone
keywords: Aligned and random nanofibrous scaffolds; Laminin; Neurotrophins; Poly-ε-caprolactone; Post-natal retinal cells; Retinal tissue engineering