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Intranasal delivery of bone marrow derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease

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posted on 03.12.2014, 15:58 by Lusine Danielyan, Sandra Beer-Hammer, Alexandra Stolzing, Richard Schafer, Georg Siegel, Claire Fabian, Philipp Kahle, Tilo Biedermann, Ali Lourhmati, Marine Buadze, Ana Novakovic, Barbara Proksch, Christoph H. Gleiter, William H. II Frey, Matthias Schwab
In view of the rapid preclinical development of cell-based therapies for neurodegenerative disorders, traumatic brain injury, and tumors, the safe and efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSCs) to the brain in the rat 6-hydroxydopamine model of Parkinson’s disease (PD). The present study examined delivery of bone marrow derived MSCs, macrophages, and microglia to the brain in a transgenic model of PD ((Thy1)-h[A30P] αS) and an APP/PS1 model of Alzheimer’s disease (AD) via intranasal application (INA). INA of microglia in naïve BL/6 mice led to targeted and effective delivery of cells to the brain. Quantitative PCR analysis of eGFP DNA showed that the brain contained the highest amount of eGFP-microglia (up to 2.1x104) after INA of 1x106 cells, while the total amount of cells detected in peripheral organs did not exceed 3.4x103. Seven days after INA, MSCs expressing eGFP were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem of (Thy1)-h[A30P] αS transgenic mice, showing predominant distribution within the OB and brainstem. INA of eGFP-expressing macrophages in 13 month-old APP/PS1 mice led to delivery of cells to the OB, hippocampus, cortex, and cerebellum. Both, MSCs and macrophages contained Iba-1-positive population of small microglia-like cells and Iba-1-negative large rounded cells showing either intracellular Amyloid beta (macrophages in APP/PS1 model) or α-Synuclein (MSCs in (Thy1)-h[A30P] αS model) immunoreactivity. Here we show, for the first time, intranasal delivery of cells to the brain of transgenic PD and AD mouse models. Additional work is needed to determine the optimal dosage (single treatment regimen or repeated administrations) to achieve functional improvement in these mouse models with intranasal microglia/macrophages and MSCs.

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

Cell Transplantation

Volume

X

Pages

1 - 10

Citation

DANIELYAN, L. ... et al, 2014. Intranasal delivery of bone marrow derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease. Cell Transplantation, 23 (supp 1), pp. S123-S139.

Publisher

© 2014 Cognizant Communication Corporation

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial 3.0 International (CC BY-NC 3.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/3.0/

Publication date

2014

Notes

This is an Open Access article, it is published by the Cognizant Communication Corporation under a Creative Commons Attribution Non-Commercial (CC BY NC) license.

ISSN

0963-6897

eISSN

1555-3892

Language

en