Effect of Intranasal Administration of Multipotent Mesenchymal Stromal Cell Exosomes on Memory of Mice in Alzheimer's Disease Model.

We studied the effect of intranasal administration of exosomes obtained by culturing of multipotent mesenchymal stromal cells (MMSC) isolated from the Wharton's jelly of the human umbilical cord on spatial memory of olfactory bulbectomized mice demonstrating the basic signs of a sporadic form of Alzheimer's disease. Intranasal administration of isolated exosomes expressing typical markers CD9, CD63 and CD81 improved spatial memory in bulbectomized animals, which manifested in a significant increase in the number of visits to the target sector and the time spent there in comparison with indifferent sectors. After administration, labeled exosomes were found in the hippocampus and neocortex, the structures playing an important role in learning and memory processes and affected by Alzheimer's disease. The advantages of exosomes in comparison with MMSC are their small size, low immunogenicity, and inability to cause cell transformation together with high therapeutic efficacy.