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Mesenchymal stem cells enhance autophagy and increase ?-amyloid clearance in Alzheimer disease models.

ABSTRACT: Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-? (A?) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of A? clearance In A?-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with A? only. Immunofluorescence revealed that MSC coculture in A?-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in A?-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with A?-treated neuronal cells. Furthermore, MSC coculture markedly increased A? immunoreactivity colocalized within lysosomes and decreased intracellular A? levels compared with A?-treated cells. In A?-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of A? in the hippocampus, which was elevated in A?-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of A? in AD models, which may lead to increased neuronal survival against A? toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment.

SUBMITTER: Shin JY 

PROVIDER: S-EPMC4389879 | biostudies-other | 2014 Jan

REPOSITORIES: biostudies-other

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Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models.

Shin Jin Young JY   Park Hyun Jung HJ   Kim Ha Na HN   Oh Se Hee SH   Bae Jae-Sung JS   Ha Hee-Jin HJ   Lee Phil Hyu PH  

Autophagy 20130101 1

Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ  ...[more]