title: Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells: comparison with human bone marrow and adipose-derived mesenchymal stem cells.
abstract: We have investigated and compared the neurotrophic activity of human dental pulp stem cells (hDPSC), human bone marrow-derived mesenchymal stem cells (hBMSC) and human adipose-derived stem cells (hAMSC) on axotomised adult rat retinal ganglion cells (RGC) in vitro in order to evaluate their therapeutic potential for neurodegenerative conditions of RGC. Using the transwell system, RGC survival and length/number of neurites were quantified in coculture with stem cells in the presence or absence of specific Fc-receptor inhibitors to determine the role of NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA and PDGF-AB/BB in stem cell-mediated RGC neuroprotection and neuritogenesis. Conditioned media, collected from cultured hDPSC/hBMSC/hAMSC, were assayed for the secreted growth factors detailed above using ELISA. PCR array determined the hDPSC, hBMSC and hAMSC expression of genes encoding 84 growth factors and receptors. The results demonstrated that hDPSC promoted significantly more neuroprotection and neuritogenesis of axotomised RGC than either hBMSC or hAMSC, an effect that was neutralized after the addition of specific Fc-receptor inhibitors. hDPSC secreted greater levels of various growth factors including NGF, BDNF and VEGF compared with hBMSC/hAMSC. The PCR array confirmed these findings and identified VGF as a novel potentially therapeutic hDPSC-derived neurotrophic factor (NTF) with significant RGC neuroprotective properties after coculture with axotomised RGC. In conclusion, hDPSC promoted significant multi-factorial paracrine-mediated RGC survival and neurite outgrowth and may be considered a potent and advantageous cell therapy for retinal nerve repair.
authors.affiliation: Neurotrauma Research Group, Neurobiology Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom; School of Dentistry, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Mead
authors.affiliation: Neurotrauma Research Group, Neurobiology Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Ann
authors.initials: A
authors.lastname: Logan
authors.affiliation: Neurotrauma Research Group, Neurobiology Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Berry
authors.affiliation: Neurotrauma Research Group, Neurobiology Section, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Wendy
authors.initials: W
authors.lastname: Leadbeater
authors.affiliation: School of Dentistry, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Scheven
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D019771:Axotomy; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D018920:Coculture Techniques; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000378:metabolism; D016501:Neurites / Q000502:physiology*; D000066829:Neuroprotection; D019899:Paracrine Communication / Q000502:physiology*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020932:Nerve Growth Factor