title: Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury.
abstract: OBJECTIVE
  To investigate the potential therapeutic benefit of intravitreally implanted dental pulp stem cells (DPSCs) on axotomized adult rat retinal ganglion cells (RGCs) using in vitro and in vivo neural injury models.
  
  
  METHODS
  Conditioned media collected from cultured rat DPSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were assayed for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) secretion using ELISA. DPSCs or BMSCs were cocultured with retinal cells, with or without Fc-TrK inhibitors, in a Transwell system, and the number of surviving βIII-tubulin⁺ retinal cells and length/number of βIII-tubulin⁺ neurites were quantified. For the in vivo study, DPSCs or BMSCs were transplanted into the vitreous body of the eye after a surgically induced optic nerve crush injury. At 7, 14, and 21 days postlesion (dpl), optical coherence tomography (OCT) was used to measure the retinal nerve fiber layer thickness as a measure of axonal atrophy. At 21 dpl, numbers of Brn-3a⁺ RGCs in parasagittal retinal sections and growth-associated protein-43⁺ axons in longitudinal optic nerve sections were quantified as measures of RGC survival and axon regeneration, respectively.
  
  
  RESULTS
  Both DPSCs and BMSCs secreted NGF, BDNF, and NT-3, with DPSCs secreting significantly higher titers of NGF and BDNF than BMSCs. DPSCs, and to a lesser extent BMSCs, promoted statistically significant survival and neuritogenesis/axogenesis of βIII-tubulin⁺ retinal cells in vitro and in vivo where the effects were abolished after TrK receptor blockade.
  
  
  CONCLUSIONS
  Intravitreal transplants of DPSCs promoted significant neurotrophin-mediated RGC survival and axon regeneration after optic nerve injury.
authors.affiliation: Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Mead
authors.forename: Ann
authors.initials: A
authors.lastname: Logan
authors.forename: Martin
authors.initials: M
authors.lastname: Berry
authors.forename: Wendy
authors.initials: W
authors.lastname: Leadbeater
authors.forename: Ben A
authors.initials: BA
authors.lastname: Scheven
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018920:Coculture Techniques; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D041623:Tomography, Optical Coherence; D014822:Vitreous Body / Q000601:surgery*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D020932:Nerve Growth Factor
keywords: axon regeneration; cell transplantation; dental pulp stem cells; mesenchymal stem cells; neuroprotection