6533b85dfe1ef96bd12bdd52

RESEARCH PRODUCT

Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats.

Baiba JansoneVladimirs PiļipenkoUgnė JonavičėZane DzirkaleVija KlusaAugustas PivoriūnasVirginijus TunaitisKarolina KriaučiūnaitėJolanta PupureAkvilė JarmalavičiūtėKarīna Narbute

subject

0301 basic medicineMaleCell signalingParkinson's diseaseParkinson's diseaseStriatumPharmacology0302 clinical medicineMedicineMedial forebrain bundleAdult stem cellsStem CellsNeurodegenerationParkinson DiseaseGeneral MedicineAnimal modelsSubstantia NigraDifferentiationmedicine.symptom:MEDICINE::Physiology and pharmacology::Pharmacological research [Research Subject Categories]Tyrosine 3-MonooxygenaseCellular therapySubstantia nigraLesion03 medical and health sciencesExtracellular VesiclesMicroscopy Electron TransmissionTissue Engineering and Regenerative MedicineAnimalsHumansRats WistarOxidopamineAdministration IntranasalAgedHydroxydopamineTyrosine hydroxylasebusiness.industryCell Biologymedicine.diseaseCorpus StriatumRatsDisease Models Animal030104 developmental biologynervous systemMesenchymal stem cellsbusinessTooth030217 neurology & neurosurgeryDevelopmental Biology

description

Abstract Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting millions of people worldwide. At present, there is no effective cure for PD; treatments are symptomatic and do not halt progression of neurodegeneration. Extracellular vesicles (EVs) can cross the blood–brain barrier and represent promising alternative to the classical treatment strategies. In the present study, we examined therapeutic effects of intranasal administration of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on unilateral 6-hydroxydopamine (6-OHDA) medial forebrain bundle (MFB) rat model of PD. CatWalk gait tests revealed that EVs effectively suppressed 6-OHDA-induced gait impairments. All tested gait parameters (stand, stride length, step cycle, and duty cycle) were significantly improved in EV-treated animals when compared with 6-OHDA-lesion group rats. Furthermore, EVs slowed down numbers of 6-OHDA-induced contralateral rotations in apomorphine test. Improvements in motor function correlated with normalization of tyrosine hydroxylase expression in the striatum and substantia nigra. In conclusion, we demonstrated, for the first time, the therapeutic efficacy of intranasal administration of EVs derived from SHEDs in a rat model of PD induced by 6-OHDA intra-MFB lesion. Our findings could be potentially exploited for the development of new treatment strategies against PD.

10.1002/sctm.18-0162https://pubmed.ncbi.nlm.nih.gov/30706999