PMID- 24150755 OWN - NLM STAT- MEDLINE DCOM- 20140124 LR - 20220311 IS - 1552-5783 (Electronic) IS - 0146-0404 (Linking) VI - 54 IP - 12 DP - 2013 Nov 15 TI - Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury. PG - 7544-56 LID - 10.1167/iovs.13-13045 [doi] AB - 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 betaIII-tubulin(+) retinal cells and length/number of betaIII-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 betaIII-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. FAU - Mead, Ben AU - Mead B AD - Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom. FAU - Logan, Ann AU - Logan A FAU - Berry, Martin AU - Berry M FAU - Leadbeater, Wendy AU - Leadbeater W FAU - Scheven, Ben A AU - Scheven BA LA - eng GR - BB/F017553/1/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131115 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neurotrophin 3) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Animals MH - Axons/*physiology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Coculture Techniques MH - Dental Pulp/*cytology/metabolism MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Male MH - Mesenchymal Stem Cells/cytology/metabolism MH - Nerve Growth Factor/metabolism MH - Nerve Regeneration/*physiology MH - Neurotrophin 3/metabolism MH - Optic Nerve Injuries/metabolism/*prevention & control MH - Rats MH - Rats, Sprague-Dawley MH - Retinal Ganglion Cells/*physiology MH - *Stem Cell Transplantation MH - Stem Cells/physiology MH - Tomography, Optical Coherence MH - Vitreous Body/*surgery OTO - NOTNLM OT - axon regeneration OT - cell transplantation OT - dental pulp stem cells OT - mesenchymal stem cells OT - neuroprotection EDAT- 2013/10/24 06:00 MHDA- 2014/01/25 06:00 CRDT- 2013/10/24 06:00 PHST- 2013/10/24 06:00 [entrez] PHST- 2013/10/24 06:00 [pubmed] PHST- 2014/01/25 06:00 [medline] AID - iovs.13-13045 [pii] AID - 10.1167/iovs.13-13045 [doi] PST - epublish SO - Invest Ophthalmol Vis Sci. 2013 Nov 15;54(12):7544-56. doi: 10.1167/iovs.13-13045.