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.
Highlights
Parkinson’s disease (PD), the second most common neurodegenerative disease after Alzheimer’s disease, is characterized by the gradual loss of dopaminergic (DA) neurons in the substantia nigra [1,2]
As examined by the Rotarod test, a well-known system to test brain function, these rotenone-treated rats exhibited significant posture instability and behavioral defects and simultaneously lost the ability to travel for a longer period on the Rotarod device (Figure 1B)
The brain from rotenone-treated rats was subjected to immunohistochemistry analysis for various PD-specific markers
Summary
Parkinson’s disease (PD), the second most common neurodegenerative disease after Alzheimer’s disease, is characterized by the gradual loss of dopaminergic (DA) neurons in the substantia nigra [1,2]. Cell replacement therapy using embryonic stem cells (ESCs) [6], mesenchymal stem cells (MSCs) [7,8], or neural stem cells [9] may provide therapeutic opportunity for neurodegenerative diseases. Cell therapy using ESCs does not always exhibit long-term efficacy, and severe side effects such as graft-induced dyskinesia have been reported in PD patients after ESC transplantation [10,11]. Recent evidence showed that administration of the conditioned medium of SHED (SHED-CM) could alleviate the severity of experimental autoimmune encephalomyelitis [18] and cognitive function in a model of Alzheimer’s disease [19]. Whether the bioactive constituents in SHED-CM exhibit therapeutic effects that can ameliorate PD symptoms remains uncertain
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