The therapeutic potential of human multipotent mesenchymal stromal cells combined with pharmacologically active microcarriers transplanted in hemi-parkinsonian rats.
Identifieur interne : 000998 ( PubMed/Corpus ); précédent : 000997; suivant : 000999The therapeutic potential of human multipotent mesenchymal stromal cells combined with pharmacologically active microcarriers transplanted in hemi-parkinsonian rats.
Auteurs : Gaëtan J-R Delcroix ; Elisa Garbayo ; Laurence Sindji ; Olivier Thomas ; Claire Vanpouille-Box ; Paul C. Schiller ; Claudia N. Montero-MeneiSource :
- Biomaterials [ 1878-5905 ] ; 2011.
English descriptors
- KwdEn :
- Animals, Behavior, Animal, Cell Differentiation (drug effects), Female, Fluorescent Antibody Technique, Humans, Lactic Acid (chemistry), Laminin (chemistry), Mesenchymal Stem Cell Transplantation (methods), Microspheres, Multipotent Stem Cells (cytology), Neurotrophin 3 (chemistry), Neurotrophin 3 (pharmacology), Parkinson Disease (metabolism), Parkinson Disease (therapy), Polyglycolic Acid (chemistry), Rats, Rats, Sprague-Dawley, Stromal Cells (cytology), Tissue Engineering (methods).
- MESH :
- chemical , chemistry : Lactic Acid, Laminin, Neurotrophin 3, Polyglycolic Acid.
- cytology : Multipotent Stem Cells, Stromal Cells.
- drug effects : Cell Differentiation.
- metabolism : Parkinson Disease.
- methods : Mesenchymal Stem Cell Transplantation, Tissue Engineering.
- chemical , pharmacology : Neurotrophin 3.
- therapy : Parkinson Disease.
- Animals, Behavior, Animal, Female, Fluorescent Antibody Technique, Humans, Microspheres, Rats, Rats, Sprague-Dawley.
Abstract
Multipotent mesenchymal stromal cells (MSCs) raise great interest for brain cell therapy due to their ease of isolation from bone marrow, their immunomodulatory and tissue repair capacities, their ability to differentiate into neuronal-like cells and to secrete a variety of growth factors and chemokines. In this study, we assessed the effects of a subpopulation of human MSCs, the marrow-isolated adult multilineage inducible (MIAMI) cells, combined with pharmacologically active microcarriers (PAMs) in a rat model of Parkinson's disease (PD). PAMs are biodegradable and non-cytotoxic poly(lactic-co-glycolic acid) microspheres, coated by a biomimetic surface and releasing a therapeutic protein, which acts on the cells conveyed on their surface and on their microenvironment. In this study, PAMs were coated with laminin and designed to release neurotrophin 3 (NT3), which stimulate the neuronal-like differentiation of MIAMI cells and promote neuronal survival. After adhesion of dopaminergic-induced (DI)-MIAMI cells to PAMs in vitro, the complexes were grafted in the partially dopaminergic-deafferented striatum of rats which led to a strong reduction of the amphetamine-induced rotational behavior together with the protection/repair of the nigrostriatal pathway. These effects were correlated with the increased survival of DI-MIAMI cells that secreted a wide range of growth factors and chemokines. Moreover, the observed increased expression of tyrosine hydroxylase by cells transplanted with PAMs may contribute to this functional recovery.
DOI: 10.1016/j.biomaterials.2010.10.041
PubMed: 21074844
Links to Exploration step
pubmed:21074844Le document en format XML
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<author><name sortKey="Garbayo, Elisa" sort="Garbayo, Elisa" uniqKey="Garbayo E" first="Elisa" last="Garbayo">Elisa Garbayo</name>
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<author><name sortKey="Sindji, Laurence" sort="Sindji, Laurence" uniqKey="Sindji L" first="Laurence" last="Sindji">Laurence Sindji</name>
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<author><name sortKey="Thomas, Olivier" sort="Thomas, Olivier" uniqKey="Thomas O" first="Olivier" last="Thomas">Olivier Thomas</name>
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<term>Fluorescent Antibody Technique</term>
<term>Humans</term>
<term>Lactic Acid (chemistry)</term>
<term>Laminin (chemistry)</term>
<term>Mesenchymal Stem Cell Transplantation (methods)</term>
<term>Microspheres</term>
<term>Multipotent Stem Cells (cytology)</term>
<term>Neurotrophin 3 (chemistry)</term>
<term>Neurotrophin 3 (pharmacology)</term>
<term>Parkinson Disease (metabolism)</term>
<term>Parkinson Disease (therapy)</term>
<term>Polyglycolic Acid (chemistry)</term>
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<front><div type="abstract" xml:lang="en">Multipotent mesenchymal stromal cells (MSCs) raise great interest for brain cell therapy due to their ease of isolation from bone marrow, their immunomodulatory and tissue repair capacities, their ability to differentiate into neuronal-like cells and to secrete a variety of growth factors and chemokines. In this study, we assessed the effects of a subpopulation of human MSCs, the marrow-isolated adult multilineage inducible (MIAMI) cells, combined with pharmacologically active microcarriers (PAMs) in a rat model of Parkinson's disease (PD). PAMs are biodegradable and non-cytotoxic poly(lactic-co-glycolic acid) microspheres, coated by a biomimetic surface and releasing a therapeutic protein, which acts on the cells conveyed on their surface and on their microenvironment. In this study, PAMs were coated with laminin and designed to release neurotrophin 3 (NT3), which stimulate the neuronal-like differentiation of MIAMI cells and promote neuronal survival. After adhesion of dopaminergic-induced (DI)-MIAMI cells to PAMs in vitro, the complexes were grafted in the partially dopaminergic-deafferented striatum of rats which led to a strong reduction of the amphetamine-induced rotational behavior together with the protection/repair of the nigrostriatal pathway. These effects were correlated with the increased survival of DI-MIAMI cells that secreted a wide range of growth factors and chemokines. Moreover, the observed increased expression of tyrosine hydroxylase by cells transplanted with PAMs may contribute to this functional recovery.</div>
</front>
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<Abstract><AbstractText>Multipotent mesenchymal stromal cells (MSCs) raise great interest for brain cell therapy due to their ease of isolation from bone marrow, their immunomodulatory and tissue repair capacities, their ability to differentiate into neuronal-like cells and to secrete a variety of growth factors and chemokines. In this study, we assessed the effects of a subpopulation of human MSCs, the marrow-isolated adult multilineage inducible (MIAMI) cells, combined with pharmacologically active microcarriers (PAMs) in a rat model of Parkinson's disease (PD). PAMs are biodegradable and non-cytotoxic poly(lactic-co-glycolic acid) microspheres, coated by a biomimetic surface and releasing a therapeutic protein, which acts on the cells conveyed on their surface and on their microenvironment. In this study, PAMs were coated with laminin and designed to release neurotrophin 3 (NT3), which stimulate the neuronal-like differentiation of MIAMI cells and promote neuronal survival. After adhesion of dopaminergic-induced (DI)-MIAMI cells to PAMs in vitro, the complexes were grafted in the partially dopaminergic-deafferented striatum of rats which led to a strong reduction of the amphetamine-induced rotational behavior together with the protection/repair of the nigrostriatal pathway. These effects were correlated with the increased survival of DI-MIAMI cells that secreted a wide range of growth factors and chemokines. Moreover, the observed increased expression of tyrosine hydroxylase by cells transplanted with PAMs may contribute to this functional recovery.</AbstractText>
<CopyrightInformation>2010 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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