Interaction of Mesenchymal Stromal Cells with 5XFAD Mouse Hippocampal Cells in Primary Culture Depending on Cocultivation Method

Abstract

We studied the mutual influence of multipotent mesenchymal stromal cells (MMSC) isolated from human umbilical cord Wharton’s jelly and primary culture of hippocampal cell from transgenic (Tg) 5XFAD mice, a model of familial Alzheimer’s disease (AD). Antibodies to human nuclear antigen were used to identify MMSCs in “chimeric culture”; the cells belonging to neurons or astrocytes were determined by the presence of positive immunoreactivity to marker proteins MAP2 and GFAP. It was shown that the result of the interaction depends on both the cocultivation method and the age of the culture. In indirect (non-contact) cocultivation, the aggressive environment of the transgenic culture affected the survival rate and impaired the adhesive properties of the MMSCs. Pretreatment of these cells with stress proteins YB-1 and HSP70, which possess neuroprotective properties, increased the resistance of MMSCs. In young culture during contact cocultivation, the MMSCs play the role of specific strands that promote grouping of hippocampal cells of transgenic mice and formation of neurospheres. In old transgenic cultures, irrespective of the cocultivation method, the MMSCs differentiated into astrocytes, but during prolonged direct cocultivation, a part of MMSCs became immunopositive to the neuronal marker MAP2. The work shows that the interaction between the MMSCs and the hippocampal cell culture can be carried out with the participation of gap junctions as well as due to the formation of nanotubes. The results obtained indicate the presence of a complex relationship between donor MMSCs and recipient cells, which must be taken into account when introducing cell therapy into the practice of treating AD patients.