Improvement of impaired motor functions by human dental exfoliated deciduous teeth stem cell-derived factors in a rat model of parkinson’s disease
Journal
International Journal of Molecular Sciences
Journal Volume
21
Journal Issue
11
Date Issued
2020
Author(s)
Abstract
Parkinson’s disease (PD) is a long-term degenerative disease of the central nervous system (CNS) that primarily affects the motor system. So far there is no effective treatment for PD, only some drugs, surgery, and comprehensive treatment can alleviate the symptoms of PD. Stem cells derived from human exfoliated deciduous teeth (SHED), mesenchymal stem cells derived from dental pulp, may have promising potential in regenerative medicine. In this study, we examine the therapeutic effect of SHED-derived conditioned medium (SHED-CM) in a rotenone-induced PD rat model. Intravenous administration of SHED-CM generated by standardized procedures significantly improved the PD symptoms accompanied with increased tyrosine hydroxylase amounts in the striatum, and decreased α-synuclein levels in both the nigra and striatum, from rotenone-treated rats. In addition, this SHED-CM treatment decreased both Iba-1 and CD4 levels in these brain areas. Gene ontology analysis indicated that the biological process of genes affected by SHED-CM was primarily implicated in neurodevelopment and nerve regeneration. The major constituents of SHED-CM included insulin-like growth factor binding protein-6 (IGFBP-6), tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-1, and transforming growth factor β1 (TGF-β1). RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) revealed that these factors may ameliorate PD symptoms through modulating the cholinergic synapses, calcium signaling pathways, serotoninergic synapses, and axon guidance. In conclusion, our data indicate that SHEDCM contains active constituents that may have promising efficacy to alleviate PD. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Human exfoliated deciduous teeth; Parkinson’s disease (PD); Rotenone; Stem cell
SDGs
Other Subjects
5' nucleotidase; alpha synuclein; bone morphogenetic protein 5; CD34 antigen; CD4 antigen; endoglin; receptor type tyrosine protein phosphatase C; rotenone; somatomedin binding protein 2; somatomedin binding protein 4; somatomedin binding protein 6; Thy 1 membrane glycoprotein; tissue inhibitor of metalloproteinase 1; tissue inhibitor of metalloproteinase 2; transforming growth factor beta1; tyrosine 3 monooxygenase; alpha synuclein; neuroprotective agent; somatomedin binding protein 6; tissue inhibitor of metalloproteinase; transforming growth factor beta; tyrosine 3 monooxygenase; animal experiment; animal model; Article; brain region; calcium signaling; child; cholinergic synapse; clinical evaluation; controlled study; corpus striatum; deciduous tooth; female; gene ontology; genetic profile; human; human tissue; ingenuity pathway analysis; male; motor dysfunction; motor performance; nerve cell differentiation; nerve regeneration; nonhuman; Parkinson disease; rat; RNA sequencing; school child; stem cell derived human exfoliated deciduous teeth; stem cell transplantation; substantia nigra; symptom; synapse; therapy effect; treatment indication; animal; cell culture; chemistry; conditioned medium; cytology; deciduous tooth; drug effect; intravenous drug administration; Lewis rat; mesenchymal stem cell; metabolism; Parkinson disease; pharmacology; alpha-Synuclein; Animals; Cells, Cultured; Corpus Striatum; Culture Media, Conditioned; Female; Humans; Injections, Intravenous; Insulin-Like Growth Factor Binding Protein 6; Mesenchymal Stem Cells; Neuroprotective Agents; Parkinson Disease; Rats; Rats, Inbred Lew; Tissue Inhibitor of Metalloproteinases; Tooth, Deciduous; Transforming Growth Factor beta; Tyrosine 3-Monooxygenase
Publisher
MDPI AG
Type
journal article