PMID- 15128393 OWN - NLM STAT- MEDLINE DCOM- 20040614 LR - 20220224 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 19 IP - 9 DP - 2004 May TI - 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. PG - 2388-98 AB - 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. FAU - Nosrat, Irina V AU - Nosrat IV AD - Department of Biologic and Materials Sciences, Room 3218, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA. nosrat@umich.edu FAU - Smith, Christopher A AU - Smith CA FAU - Mullally, Patrick AU - Mullally P FAU - Olson, Lars AU - Olson L FAU - Nosrat, Christopher A AU - Nosrat CA LA - eng GR - R03 DE014455-01A1/DE/NIDCR NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA, Complementary) RN - 0 (GDNF protein, human) RN - 0 (Gdnf protein, rat) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Iodine Isotopes) RN - 0 (Nerve Growth Factors) RN - 0 (RNA, Messenger) RN - 0 (Tubulin) RN - 0 (UCHL1 protein, human) RN - 8HW4YBZ748 (Oxidopamine) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 3.4.19.12 (Ubiquitin Thiolesterase) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Adolescent MH - Adult MH - Animals MH - Animals, Newborn MH - Antibodies/pharmacology MH - Brain-Derived Neurotrophic Factor/genetics/immunology/metabolism MH - Cell Count/methods MH - Cell Differentiation/*physiology MH - Cell Division/drug effects/physiology MH - Cell Survival/physiology MH - Cells, Cultured MH - Coculture Techniques/methods MH - DNA, Complementary/chemistry MH - Dental Pulp/cytology/innervation/*physiology MH - Dopamine/*metabolism MH - Embryo, Mammalian MH - Female MH - Glial Cell Line-Derived Neurotrophic Factor MH - Humans MH - Immunohistochemistry/methods MH - Iodine Isotopes/pharmacokinetics MH - Male MH - Mesencephalon/cytology MH - Nerve Growth Factor/genetics/immunology/metabolism MH - Nerve Growth Factors/pharmacokinetics/*physiology MH - Neurons/drug effects/*metabolism MH - Oxidopamine/toxicity MH - Pregnancy MH - Pseudopodia/metabolism MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Time Factors MH - Tissue Engineering MH - Tooth/embryology/innervation MH - Tubulin/metabolism MH - Tyrosine 3-Monooxygenase/metabolism MH - Ubiquitin Thiolesterase/metabolism MH - Vibrissae/embryology/innervation EDAT- 2004/05/07 05:00 MHDA- 2004/06/15 05:00 CRDT- 2004/05/07 05:00 PHST- 2004/05/07 05:00 [pubmed] PHST- 2004/06/15 05:00 [medline] PHST- 2004/05/07 05:00 [entrez] AID - EJN3314 [pii] AID - 10.1111/j.0953-816X.2004.03314.x [doi] PST - ppublish SO - Eur J Neurosci. 2004 May;19(9):2388-98. doi: 10.1111/j.0953-816X.2004.03314.x.