Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury

Ben Mead*, Ann Logan, Martin Berry, Wendy Leadbeater, Ben A. Scheven

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Purpose. 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.

Original languageEnglish
Pages (from-to)7544-7556
Number of pages13
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number12
DOIs
Publication statusPublished - 22 Oct 2013

Bibliographical note

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Keywords

  • Axon regeneration
  • Cell transplantation
  • Dental pulp stem cells
  • Mesenchymal stem cells
  • Neuroprotection

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