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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of parkinson disease
Rejuvenation Research, Volume 14, No. 1, Year 2011
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Description
Safe and effective cell delivery remains one of the main challenges in cell-based therapy of neurodegenerative disorders. Graft survival, sufficient enrichment of therapeutic cells in the brain, and avoidance of their distribution throughout the peripheral organs are greatly influenced by the method of delivery. Here we demonstrate for the first time noninvasive intranasal (IN) delivery of mesenchymal stem cells (MSCs) to the brains of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. IN application (INA) of MSCs resulted in the appearance of cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1×106 MSCs applied intranasally, 24% survived for at least 4.5 months in the brains of 6-OHDA rats as assessed by quantification of enhanced green fluorescent protein (EGFP) DNA. Quantification of proliferating cell nuclear antigen-positive EGFP-MSCs showed that 3% of applied MSCs were proliferative 4.5 months after application. INA of MSCs increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase in terminal deoxynucleotidyl transferase (TdT)-mediated 2′-deoxyuridine, 5′-triphosphate (dUTP)-biotin nick end labeling (TUNEL) staining of these areas. INA of EGFP-labeled MSCs prevented any decrease in the dopamine level in the lesioned hemisphere, whereas the lesioned side of the control animals revealed significantly lower levels of dopamine 4.5 months after 6-OHDA treatment. Behavioral analyses revealed significant and substantial improvement of motor function of the Parkinsonian forepaw to up to 68% of the normal value 40-110 days after INA of 1×106 cells. MSC-INA decreased the concentrations of inflammatory cytokines-interleukin-1β (IL-1β), IL-2, -6, -12, tumor necrosis factor (TNF), interferon-γ (IFN-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF)-in the lesioned side to their levels in the intact hemisphere. IN administration provides a highly promising noninvasive alternative to the traumatic surgical procedure of transplantation and allows targeted delivery of cells to the brain with the option of chronic application. © 2011 Mary Ann Liebert, Inc.
Authors & Co-Authors
Danielyan, Lusine
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Schäfer, Richard
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
United States, Cambridge
Harvard Stem Cell Institute
Von Ameln-Mayerhofer, Andreas
Germany, Tubingen
Eberhard Karls Universität Tübingen
Bernhard, Felix
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Verleysdonk, Stephan
Germany, Tubingen
Eberhard Karls Universität Tübingen
Egypt, New Cairo
German University in Cairo
Buadze, Marine
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Lourhmati, Ali
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Klopfer, Tim
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Schaumann, Felix
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Schmid, Barbara
Germany, Tubingen
Eberhard Karls Universität Tübingen
Koehle, Christoph
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Proksch, Barbara
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Weissert, Robert
Germany, Tubingen
Eberhard Karls Universität Tübingen
Switzerland, Geneva
Université de Genève
Reichardt, Holger M.
Germany, Gottingen
Universitätsmedizin Göttingen
Van Den Brandt, Jens
Germany, Gottingen
Universitätsmedizin Göttingen
Buniatian, Gayane H.
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Armenia, Yerevan
Institute of Molecular Biology of the National Academy of Sciences of Armenia
Schwab, Matthias M.
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Germany, Tubingen
Eberhard Karls Universität Tübingen
Gleiter, Christoph H.
Germany, Tubingen
Universitätsklinikum Und Medizinische Fakultät Tübingen
Frey, W. H.II
United States, Minneapolis
Regions Hospital
Statistics
Citations: 233
Authors: 19
Affiliations: 8
Identifiers
Doi:
10.1089/rej.2010.1130
ISSN:
15491684
Research Areas
Cancer
Genetics And Genomics
Health System And Policy