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

Simon C 1 , Gan QF 2 , Kathivaloo P 3 , Mohamad NA 4 , Dhamodharan J 5 , Krishnan A 6 Show all authors , Sengodan B 7 , Palanimuthu VR 8 , Marimuthu K 9 , Rajandas H 10 , Ravichandran M 11 , Parimannan S 12

Affiliations 

  • 1 Brain Research Institute, School of Medicine and Health Sciences, Monash University, Sunway Campus, Selangor 47500, Malaysia. Christopher.simon@monash.edu
  • 2 Anatomy Unit, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah 08100, Malaysia. qfganptana@outlook.com
  • 3 Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Semeling, Bedong, Kedah 08100, Malaysia. prema@meluhagroup.com
  • 4 Department of Biotechnology, Faculty of Applied Sciences, AIMST University, Semeling, Bedong, Kedah 08100, Malaysia. afiqah@meluhagroup.com
  • 5 Anatomy Unit, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah 08100, Malaysia. jagadeesh@aimst.edu.my
  • 6 Anatomy Unit, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah 08100, Malaysia. arulmoli@aimst.edu.my
  • 7 Pathology Unit, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah 08100, Malaysia. bharathi@aimst.edu.my
  • 8 School of Pharmacy, Queen's University Belfast, Northern Ireland BT9 7BL, UK. V.Palanimuthu@qub.ac.uk
  • 9 Centre of Excellence for Omics-Driven Computational Biodiscovery, AIMST University, Bedong, Kedah 08100, Malaysia. aquamuthu2k@gmail.com
  • 10 Centre of Excellence for Omics-Driven Computational Biodiscovery, AIMST University, Bedong, Kedah 08100, Malaysia. heraadaas@gmail.com
  • 11 Centre of Excellence for Omics-Driven Computational Biodiscovery, AIMST University, Bedong, Kedah 08100, Malaysia. ravichandran@aimst.edu.my
  • 12 Centre of Excellence for Omics-Driven Computational Biodiscovery, AIMST University, Bedong, Kedah 08100, Malaysia. sivachandran@aimst.edu.my
Int J Mol Sci, 2019 Jan 29;20(3).
PMID: 30699944 DOI: 10.3390/ijms20030568

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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