title: Influence of alginate cross-linking method on neurite response to microencapsulated neurotrophin-producing fibroblasts.
abstract: Transplantation of cells genetically modified to produce neurotrophins is a promising spinal cord repair strategy. Previously we showed that fibroblasts engineered to produce brain-derived neurotrophic factor (Fb/BDNF) microencapsulated in alginate survive, continue to grow and express bioactive BDNF. We here compared the effects of different alginate crosslinkers on dorsal root ganglia (DRG) neurite growth using alginate-encapsulated Fb/BDNF. Aqueous sodium alginate (±Fb/BDNF) was contacted with different calcium salts, and used as substrate for DRG growth. Length, number and orientation of neurites were measured. Chloride or carbonate salts promoted significantly more neurite growth than sulphate, with or without Fb/BDNF, although encapsulated Fb/BDNF stimulated significantly more neurite growth than cell-free. An Fb/BDNF-derived neurotrophin concentration gradient directionally guided DRG neurite growth. This positive effect of alginate-encapsulated Fb/BDNF on neurite growth/guidance shows promise for enhanced regeneration and guidance of axons towards a specific target in the injured spinal cord.
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
authors: Nicola L
authors: NL
authors: Francis
authors: Mihir S
authors: MS
authors: Shanbhag
authors: Itzhak
authors: I
authors: Fischer
authors: Margaret A
authors: MA
authors: Wheatley
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000627:therapeutic use; D003432:Cross-Linking Reagents; D004339:Drug Compounding; D005347:Fibroblasts / Q000378:metabolism*; D005727:Ganglia, Spinal; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000096:biosynthesis / Q000627:therapeutic use; D009416:Nerve Regeneration; D016501:Neurites / Q000187:drug effects*; D058630:Spinal Cord Regeneration
chemical_list: D000464:Alginates; D019208:Brain-Derived Neurotrophic Factor; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D009414:Nerve Growth Factors; D020723:Glucuronic Acid