title: Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis.
abstract: OBJECTIVE
  Stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs) have unique neurogenic properties that could be potentially exploited for therapeutic use. The importance of paracrine SHED signaling for neuro-regeneration has been recognized, but the exact mechanisms behind these effects are presently unknown. In the present study, we investigated the neuro-protective potential of exosomes and micro-vesicles derived from SHEDs on human dopaminergic neurons during oxidative stress-induced by 6-hydroxy-dopamine (6-OHDA).
  
  
  METHODS
  ReNcell VM human neural stem cells were differentiated into dopaminergic neurons and treated with 100 μmol/L of 6-OHDA alone or in combination with exosomes or micro-vesicles purified by ultracentrifugation from SHEDs cultivated in serum-free medium under two conditions: in standard two-dimensional culture flasks or on laminin-coated micro-carriers in a bioreactor. Real-time monitoring of apoptosis was performed with the use of time-lapse confocal microscopy and the CellEvent Caspase-3/7 green detection reagent.
  
  
  RESULTS
  Exosomes but not micro-vesicles derived from SHEDs grown on the laminin-coated three-dimensional alginate micro-carriers suppressed 6-OHDA-induced apoptosis in dopaminergic neurons by approximately 80% throughout the culture period. Strikingly, no such effects were observed for the exosomes derived from SHEDs grown under standard culture conditions.
  
  
  CONCLUSIONS
  Our results suggest that exosomes derived from SHEDs are considered as new potential therapeutic tool in the treatment of Parkinson's disease.
authors.affiliation: Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania; Department of Neurobiology and Biophysics, Faculty of Natural Sciences, Vilnius University, Vilnius, Lithuania.
authors.forename: Akvilė
authors.initials: A
authors.lastname: Jarmalavičiūtė
authors.affiliation: Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
authors.forename: Virginijus
authors.initials: V
authors.lastname: Tunaitis
authors.affiliation: Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
authors.forename: Ugnė
authors.initials: U
authors.lastname: Pivoraitė
authors.affiliation: Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
authors.forename: Algirdas
authors.initials: A
authors.lastname: Venalis
authors.affiliation: Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. Electronic address: a.pivoriunas@imcentras.lt.
authors.forename: Augustas
authors.initials: A
authors.lastname: Pivoriūnas
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D055252:Cell-Derived Microparticles / Q000637:transplantation*; D002478:Cells, Cultured; D002648:Child; D003782:Dental Pulp / Q000166:cytology*; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism; D055354:Exosomes / Q000637:transplantation*; D006801:Humans; D008297:Male; D009416:Nerve Regeneration; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000628:therapy; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014094:Tooth, Deciduous / Q000166:cytology
chemical_list: D018696:Neuroprotective Agents; D016627:Oxidopamine; D053148:Caspase 3
keywords: 6-hydroxy-dopamine; Parkinson's disease; SHED; exosomes