title: Dental pulp cells provide neurotrophic support for dopaminergic neurons and differentiate into neurons in vitro; implications for tissue engineering and repair in the nervous system.
abstract: Glial cell line-derived neurotrophic factor (GDNF) mRNA is highly expressed by dental pulp cells (DPCs) prior to the initiation of dental pulp innervation. We show that radioactively labelled exogenous GDNF is retrogradely transported from neonatal teeth and vibrissae to the trigeminal neurons, indicating that GDNF acts as a classical neurotrophic factor in the trigeminal system. We also show that DPCs from both rats and humans produce nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and GDNF mRNAs in vitro, promote the survival and phenotypic characteristics of embryonic dopaminergic (DA) neurons and protect DA neurons against the neurotoxin 6-hydroxy-dopamine (6-OHDA) in vitro. By using inhibitory antibodies to NGF, BDNF and GDNF, we show that the promotion of DA neuron survival relates to the production and release of neurotrophic proteins by DPCs in vitro. We suggest that in vivo production of neurotrophic factors by DPCs play roles in tooth innervation. However, continued production of neurotrophic factors by the DPCs might have wider implications. We propose that the dental pulp is a viable source of easily attainable cells with possible potential for development of autologous cell transplantation therapies. We also show that a population of neural crest-derived dental pulp cells acquire clear neuronal morphology and protein expression profile in vitro, indicating the presence of a cell population in the dental pulp with neuronal differentiation capacity that might provide additional benefits when grafted into the CNS.
authors.affiliation: Department of Biologic and Materials Sciences, Room 3218, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA. nosrat@umich.edu
authors.forename: Irina V
authors.initials: IV
authors.lastname: Nosrat
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Smith
authors.forename: Patrick
authors.initials: P
authors.lastname: Mullally
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Nosrat
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D018076:DNA, Complementary / Q000737:chemistry; D003782:Dental Pulp / Q000166:cytology / Q000294:innervation / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D020932:Nerve Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009414:Nerve Growth Factors / Q000493:pharmacokinetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D011247:Pregnancy; D011554:Pseudopodia / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D023822:Tissue Engineering; D014070:Tooth / Q000196:embryology / Q000294:innervation; D014404:Tubulin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D014738:Vibrissae / Q000196:embryology / Q000294:innervation
chemical_list: D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D018076:DNA, Complementary; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007456:Iodine Isotopes; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D014404:Tubulin; C482860:UCHL1 protein, human; D016627:Oxidopamine; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D043222:Ubiquitin Thiolesterase; D004298:Dopamine