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Intranasal administration of mesenchymal stem cells ameliorates the abnormal dopamine transmission system and inflammatory reaction in the R6/2 mouse model of Huntington disease

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journal contribution
posted on 19.08.2019, 14:58 by Libo Yu-Taeger, Janice Stricker-Shaver, Katrin Arnold, Patrycja Bambynek-Dziuk, Arianna Novati, Elisabeth Singer, Ali Lourhmati, Claire Fabian, Janine Magg, Olaf Riess, Matthias Schwab, Alexandra StolzingAlexandra Stolzing, Lusine Danielyan, Hoa Huu Phuc Nguyen
Intrastriatal administration of mesenchymal stem cells (MSCs) has shown beneficial effects in rodent models of Huntington disease (HD). However, the invasive nature of surgical procedure and its potential to trigger the host immune response may limit its clinical use. Hence, we sought to evaluate the non-invasive intranasal administration (INA) of MSC delivery as an effective alternative route in HD. GFP-expressing MSCs derived from bone marrow were intranasally administered to 4-week-old R6/2 HD transgenic mice. MSCs were detected in the olfactory bulb, midbrain and striatum five days post-delivery. Compared to phosphate-buffered saline (PBS)-treated littermates, MSC-treated R6/2 mice showed an increased survival rate and attenuated circadian activity disruption assessed by locomotor activity. MSCs increased the protein expression of DARPP-32 and tyrosine hydroxylase (TH) and downregulated gene expression of inflammatory modulators in the brain 7.5 weeks after INA. While vehicle treated R6/2 mice displayed decreased Iba1 expression and altered microglial morphology in comparison to the wild type littermates, MSCs restored both, Iba1 level and the thickness of microglial processes in the striatum of R6/2 mice. Our results demonstrate significantly ameliorated phenotypes of R6/2 mice after MSCs administration via INA, suggesting this method as an effective delivering route of cells to the brain for HD therapy.

Funding

BMBF (Bundesministerium für Bildung und Forschung)

Grant no. 031A575 (Project RESTRAIN)

Robert Bosch Stiftung, Stuttgart, Germany

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

Cells

Volume

8

Issue

6

Publisher

MDPI

Version

VoR (Version of Record)

Rights holder

© The authors

Acceptance date

13/06/2019

Publication date

2019-06-15

Copyright date

2019

eISSN

2073-4409

Language

en

Depositor

Prof Alexandra Stolzing

Article number

595