PMID- 25863132 OWN - NLM STAT- MEDLINE DCOM- 20160218 LR - 20200325 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1613 DP - 2015 Jul 10 TI - Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats. PG - 59-72 LID - S0006-8993(15)00289-9 [pii] LID - 10.1016/j.brainres.2015.04.001 [doi] AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of nigrostriatal dopaminergic (DAergic) neurons and the depletion of striatal dopamine. Here we show that DAergic-neuron-like cells could be efficiently induced from stem cells derived from human exfoliated deciduous teeth (SHEDs), and that these induced cells had therapeutic benefits in a 6-OHDA-induced Parkinsonian rat model. In our protocol, EGF and bFGF signaling activated the SHED's expression of proneural genes, Ngn2 and Mash1, and subsequent treatment with brain-derived neurotrophic factor (BDNF) promoted their maturation into DAergic neuron-like SHEDs (dSHEDs). A hypoxic DAergic differentiation protocol improved cell viability and enhanced the expression of multiple neurotrophic factors, including BDNF, GDNF, NT-3, and HGF. Engrafted dSHEDs survived in the striatum of Parkinsonian rats, improved the DA level more efficiently than engrafted undifferentiated SHEDs, and promoted the recovery from neurological deficits. Our findings further suggested that paracrine effects of dSHEDs contributed to neuroprotection against 6-OHDA-induced neurodegeneration and to nigrostriatal tract restoration. In addition, we found that the conditioned medium derived from dSHEDs protected primary neurons against 6-OHDA toxicity and accelerated neurite outgrowth in vitro. Thus, our data suggest that stem cells derived from dental pulp may have therapeutic benefits for PD. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Fujii, Hiromi AU - Fujii H AD - Departments of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Matsubara, Kohki AU - Matsubara K AD - Departments of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Sakai, Kiyoshi AU - Sakai K AD - Departments of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Ito, Mikako AU - Ito M AD - Departments of Neurogenetics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Ohno, Kinji AU - Ohno K AD - Departments of Neurogenetics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Ueda, Minoru AU - Ueda M AD - Departments of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. FAU - Yamamoto, Akihito AU - Yamamoto A AD - Departments of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: akihito@med.nagoya-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150409 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Ascl1 protein, rat) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurog2 protein, rat) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 62229-50-9 (Epidermal Growth Factor) SB - IM MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/metabolism MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Differentiation MH - Cell Survival MH - Child MH - Dopaminergic Neurons/*cytology/metabolism/*physiology MH - Epidermal Growth Factor/pharmacology MH - Fibroblast Growth Factor 2/pharmacology MH - Humans MH - Nerve Tissue Proteins/metabolism MH - Neural Stem Cells/metabolism/*physiology/transplantation MH - Parkinson Disease/*surgery MH - Rats MH - Tooth, Deciduous/*cytology/drug effects OTO - NOTNLM OT - Dopaminergic (DAergic) neurons OT - Neuroprotection OT - Neurotrophic factors OT - Parkinson's disease OT - Stem cells derived from human exfoliated deciduous teeth (SHEDs) OT - Transplantation EDAT- 2015/04/12 06:00 MHDA- 2016/02/19 06:00 CRDT- 2015/04/12 06:00 PHST- 2014/09/29 00:00 [received] PHST- 2015/03/31 00:00 [revised] PHST- 2015/04/01 00:00 [accepted] PHST- 2015/04/12 06:00 [entrez] PHST- 2015/04/12 06:00 [pubmed] PHST- 2016/02/19 06:00 [medline] AID - S0006-8993(15)00289-9 [pii] AID - 10.1016/j.brainres.2015.04.001 [doi] PST - ppublish SO - Brain Res. 2015 Jul 10;1613:59-72. doi: 10.1016/j.brainres.2015.04.001. Epub 2015 Apr 9.