title: Effect of dental pulp stem cells in MPTP-induced old-aged mice model.
abstract: BACKGROUND
  Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic (DA-ergic) neurons in the substantia nigra (SN) and represented as a huge threat to the geriatric population. Cell replacement therapies (CRTs) have been proposed as a promising strategy to slow down or replace neuronal loss. Among the widely available cell sources, dental pulp stem cells (DPSCs) portray as an attractive source primarily due to their neural crest origin, ease of tissue procurement and less ethical hurdles.
  
  
  METHODS
  We first demonstrated the in vitro differentiation ability of DPSCs towards DA-ergic-like cells before evaluating their neuro-protection/neuro-restoration capacities in MPTP-induced mice. Transplantation via intrathecal was performed with behavioural assessments being evaluated every fortnight. Subsequent analysis investigating their immuno-modulatory behaviour was conducted using neuronal and microglial cell lines.
  
  
  RESULTS
  It was apparent that the behavioural parameters began to improve corresponding to tyrosine hydroxylase (TH), dopamine transporter (DAT) and dopamine decarboxylase (AADC) immunostaining in SN and striatum as early as 8-week post-transplantation (P < 0·05). About 60% restoration of DA-ergic neurons was observed at SN in MPTP-treated mice after 12-week post-transplantation. Similarly, their ability to reduce toxic effects of MPTP (DNA damages, reactive oxygen species and nitric oxide release) and regulate cytokine levels was distinctly noted (P < 0·05) upon exposure in in vitro model.
  
  
  CONCLUSIONS
  Our results suggest that DPSCs may provide a therapeutic benefit in the old-aged PD mice model and may be explored in stem cell-based CRTs especially in geriatric population as an attempt towards 'personalized medicine'.
authors.affiliation: Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nareshwaran
authors.identifier: http://orcid.org/0000-0003-1550-4538
authors.initials: N
authors.lastname: Gnanasegaran
authors.affiliation: Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Vijayendran
authors.initials: V
authors.lastname: Govindasamy
authors.affiliation: Faculty of Applied Sciences, AIMST University, Semeling, Bedong, Kedah, Malaysia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Simon
authors.affiliation: Faculty of Applied Sciences, AIMST University, Semeling, Bedong, Kedah, Malaysia.
authors.forename: Quan Fu
authors.initials: QF
authors.lastname: Gan
authors.affiliation: Oral Cancer Research and Coordinating Center (OCRCC), Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Vui King
authors.initials: VK
authors.lastname: Vincent-Chong
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, Saudi Arabia.
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Mani
authors.affiliation: Department of Pharmacology, SRM College of Pharmacy, SRM University, Kattankulathur, Tamil Nadu, India.
authors.forename: Kesavanarayanan
authors.initials: K
authors.lastname: Krishnan Selvarajan
authors.affiliation: Laboratory Animal Facility and Management (LAFAM), Faculty of Pharmacy, UiTM Puncak, Alam Selangor, Malaysia.
authors.forename: Vellayan
authors.initials: V
authors.lastname: Subramaniam
authors.affiliation: Department of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sabri
authors.initials: S
authors.lastname: Musa
authors.affiliation: Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Noor Hayaty
authors.initials: NH
authors.lastname: Abu Kasim
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003342:Corpus Striatum / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology*; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008606:Mental Processes / Q000502:physiology; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010300:Parkinson Disease / Q000628:therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase
keywords: Efficacy; PKH26; immuno-modulation; intrathecal; neuro-restoration