Abstract
BackgroundMesenchymal stem cells (MSCs) have been explored as promising tools for treatment of several neurological and neurodegenerative diseases. MSCs release abundant extracellular vesicles (EVs) containing a variety of biomolecules, including mRNAs, miRNAs, and proteins. We hypothesized that EVs derived from human Wharton’s jelly would act as mediators of the communication between hMSCs and neurons and could protect hippocampal neurons from damage induced by Alzheimer’s disease-linked amyloid beta oligomers (AβOs).MethodsWe isolated and characterized EVs released by human Wharton’s jelly mesenchymal stem cells (hMSC-EVs). The neuroprotective action of hMSC-EVs was investigated in primary hippocampal cultures exposed to AβOs.ResultshMSC-EVs were internalized by hippocampal cells in culture, and this was enhanced in the presence of AβOs in the medium. hMSC-EVs protected hippocampal neurons from oxidative stress and synapse damage induced by AβOs. Neuroprotection by hMSC-EVs was mediated by catalase and was abolished in the presence of the catalase inhibitor, aminotriazole.ConclusionshMSC-EVs protected hippocampal neurons from damage induced by AβOs, and this was related to the transfer of enzymatically active catalase contained in EVs. Results suggest that hMSC-EVs should be further explored as a cell-free therapeutic approach to prevent neuronal damage in Alzheimer’s disease.
Highlights
Mesenchymal stem cells (MSCs) have been explored as promising tools for treatment of several neurological and neurodegenerative diseases
We recently reported that extracellular vesicles (EVs) derived from rat bone marrow MSCs prevent oxidative stress and synapse damage induced by Amyloid-β oligomer (AβO) in hippocampal neurons [9]
AβOs promote uptake of human Wharton’s jelly mesenchymal stem cells (hMSCs)-EVs by hippocampal cells To determine whether hMSC-EVs could be internalized by cultured hippocampal cells, we used EVs isolated from hMSCs that had been double-labeled with Vybrant DiI and SYTO RNA
Summary
Mesenchymal stem cells (MSCs) have been explored as promising tools for treatment of several neurological and neurodegenerative diseases. Converging evidence accumulated in the past 20 years indicates that soluble oligomers of the amyloid-β peptide (AβOs), toxins that accumulate in AD brains, are implicated in brain damage and dysfunction, including neuronal tau hyperphosphorylation, changes in calcium homeostasis, increased production of reactive oxygen species (ROS), mitochondrial dysfunction, and aberrant activation of microglia and astrocytes (reviewed in [3,4,5]). These events result in a degenerative process that leads to synapse failure and cognitive deficits in AD.
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