Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease

Abstract

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment. The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease. Alzheimer’s disease mouse models were established by injection of beta amyloid 1−42 aggregates into dentate gyrus bilaterally. Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration. Afterwards, neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies. Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1−42-induced cognitive impairment, and these effects are similar to those shown in the mesenchymal stem cells. These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease. All procedures and experiments were approved by Institutional Animal Care and Use Committee (CICUAL) (approval No. CICUAL 2016-011) on April 25, 2016.

Keywords

• Alzheimer′s disease; neurodegenerative disease; cognitive impairment; memory; Alzheimer′s disease mouse model; mesenchymal stem cell; exosomes; neurogenesis; cognitive improvement; cell-free therapy; neural regeneration