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

Date
2019-04-22
Authors
Narbute, Karīna
Piļipenko, Vladimirs
Pupure, Jolanta
Dzirkale, Zane
Jonavičė, Ugnė
Tunaitis, Virginijus
Kriaučiūnaitė, Karolina
Jarmalavičiūtė, Akvilė
Jansone, Baiba
Kluša, Vija
Journal Title
Journal ISSN
Volume Title
Publisher
AlphaMed Press Wiley
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.
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Keywords
Adult stem cells , Animal models , Cell signaling , Cellular therapy , Differentiation , Parkinson's disease , Mesenchymal stem cells , Research Subject Categories::MEDICINE::Physiology and pharmacology::Pharmacological research
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