Improvement of Impaired Motor Functions by Human Dental Exfoliated Deciduous Teeth Stem Cell-Derived Factors in a Rat Model of Parkinson’s Disease

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 SHED-CM contains active constituents that may have promising efficacy to alleviate PD.

Neural-Induced Human Adipose Tissue-Derived Stem Cells Conditioned Medium Ameliorates Rotenone-Induced Toxicity in SH-SY5Y Cells

“…NI-hADSC-CM likely preserved the levels of the soluble monomeric form of the α-syn protein and its physiological functions. Therefore, the inhibitory effect of NI-hADSC-CM on the levels of α-syn oligomers might be due to its active constituents, which penetrate the BBB to ameliorate the ROT-induced impairments, as previously reported [ 53 ]. We hypothesize that the reduction of the levels of insoluble oligomeric p-S129 and total α-syn, along with the preservation of the levels of soluble α-syn, may be sensitive markers for the treatment of LBs in PD.…”

Dental-Derived Mesenchymal Stem Cells: State of the Art

“…Furthermore, DMSCs have the potential to restore neurons in neurodegenerative diseases of the central nervous system (CNS), such as Alzheimer's disease (AD) (Mita et al, 2015;Wang F. et al, 2017) and Parkinson's disease (PD) (Chen et al, 2020b). DPSCs could inhibit the phosphorylation of tau protein and promote the proliferation of neural stem cells in an animal model of AD (Wang F. et al, 2017).…”

Comparative study between bone marrow mesenchymal stem cell and their conditioned medium in the treatment of rat model of Parkinsonism

“…This study showed the superiority of the conditioned medium. Also, the current histological results revealed the presence of shrunken cells with darkly stained nuclei especially after stem cell treatment (Chen et al, 2020).…”