Deciduous DPSCs Ameliorate MPTP-Mediated Neurotoxicity, Sensorimotor Coordination and Olfactory Function in Parkinsonian Mice

Parkinson’s disease (PD) is a neurodegenerative disorder defined by progressive deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dental pulp stem cells (DPSCs) have been proposed to replace the degenerated dopaminergic neurons due to its inherent neurogenic and reg...

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Vydáno v:International journal of molecular sciences Ročník 20; číslo 3; s. 568
Hlavní autoři: Simon, Christopher, Gan, Quan Fu, Kathivaloo, Premasangery, Mohamad, Nur Afiqah, Dhamodharan, Jagadeesh, Krishnan, Arulmoli, Sengodan, Bharathi, Palanimuthu, Vasanth Raj, Marimuthu, Kasi, Rajandas, Heera, Ravichandran, Manickam, Parimannan, Sivachandran
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland MDPI AG 29.01.2019
MDPI
Témata:
Bone marrow
Gene expression
Morphology
Neurons
Stem cells
intranasal delivery
MPTP
behavioural analysis
Parkinson’s disease
dental pulp stem cells
tyrosine hydroxylase
ISSN:1422-0067, 1661-6596, 1422-0067
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Shrnutí:Parkinson’s disease (PD) is a neurodegenerative disorder defined by progressive deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dental pulp stem cells (DPSCs) have been proposed to replace the degenerated dopaminergic neurons due to its inherent neurogenic and regenerative potential. However, the effective delivery and homing of DPSCs within the lesioned brain has been one of the many obstacles faced in cell-based therapy of neurodegenerative disorders. We hypothesized that DPSCs, delivered intranasally, could circumvent these challenges. In the present study, we investigated the therapeutic efficacy of intranasally administered DPSCs in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Human deciduous DPSCs were cultured, pre-labelled with PKH 26, and intranasally delivered into PD mice following MPTP treatment. Behavioural analyses were performed to measure olfactory function and sensorimotor coordination, while tyrosine hydroxylase (TH) immunofluorescence was used to evaluate MPTP neurotoxicity in SNpc neurons. Upon intranasal delivery, degenerated TH-positive neurons were ameliorated, while deterioration in behavioural performances was significantly enhanced. Thus, the intranasal approach enriched cell delivery to the brain, optimizing its therapeutic potential through its efficacious delivery and protection against dopaminergic neuron degeneration.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20030568