Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons
Identifieur interne : 000441 ( Ncbi/Checkpoint ); précédent : 000440; suivant : 000442Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons
Auteurs : Christoph Proschel [États-Unis] ; Jennifer. Stripay [États-Unis] ; Chung Shih [États-Unis] ; Joshua. Munger [États-Unis] ; Mark. Noble [États-Unis]Source :
- EMBO Molecular Medicine [ 1757-4676 ] ; 2014.
Abstract
In addition to dopaminergic neuron loss, it is clear that Parkinson disease includes other pathological changes, including loss of additional neuronal populations. As a means of addressing multiple pathological changes with a single therapeutically-relevant approach, we employed delayed transplantation of a unique class of astrocytes, GDAsBMP, that are generated
Url:
DOI: 10.1002/emmm.201302878
PubMed: 24477866
PubMed Central: 3992077
Affiliations:
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<front><div type="abstract" xml:lang="en"><p>In addition to dopaminergic neuron loss, it is clear that Parkinson disease includes other pathological changes, including loss of additional neuronal populations. As a means of addressing multiple pathological changes with a single therapeutically-relevant approach, we employed delayed transplantation of a unique class of astrocytes, GDAs<sup>BMP</sup>
, that are generated <italic>in vitro</italic>
by directed differentiation of glial precursors. GDAs<sup>BMP</sup>
produce multiple agents of interest as treatments for PD and other neurodegenerative disorders, including BDNF, GDNF, neurturin and IGF1. GDAs<sup>BMP</sup>
also exhibit increased levels of antioxidant pathway components, including levels of NADPH and glutathione. Delayed GDA<sup>BMP</sup>
transplantation into the 6-hydroxydopamine lesioned rat striatum restored tyrosine hydroxylase expression and promoted behavioral recovery. GDA<sup>BMP</sup>
transplantation also rescued pathological changes not prevented in other studies, such as the rescue of parvalbumin<sup>+</sup>
GABAergic interneurons. Consistent with expression of the synaptic modulatory proteins thrombospondin-1 and 2 by GDAs<sup>BMP</sup>
, increased expression of the synaptic protein synaptophysin was also observed. Thus, GDAs<sup>BMP</sup>
offer a multimodal support cell therapy that provides multiple benefits without requiring prior genetic manipulation.</p>
</div>
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