Interaction of Mesenchymal Stromal Cells with Primary 5XFAD Mice Hippocampus Culture Depending on Cocultivation Method

Abstract

In this work we studied the mutual influence of multipotent mesenchymal stromal cells (MMSC) isolated from Wharton’s jelly of human umbilical cord and primary culture of hippocampal cells obtained from transgenic mice 5XFAD, used as an animal model of inherited form of Alzheimer’s disease (AD). Experimental protocols included both direct and indirect co-cultivation of MMSCs with hippocampal cells from transgenic animals. It was shown that in the conditions of indirect co-culture, the aggressive environment of cultured transgenic cells significantly decreases the survival rate and adhesiveness of MMSCs. However, preliminary priming of MMSCs with proteins YB-1 and HSP70 improved the survival and adhesive properties of MMSCs. It was also found that the interactions of MMSCs with cultured hippocampal cells depend on cell culture age. Old cultures of transgenic cells induced differentiation of MMSC into astrocytes, both during direct and indirect co-cultivation. In contrast, in young cultures of transgenic cells, during contact co-cultivation, MMSCs played the role of specific strands that promoted clustering of hippocampal cells in the culture and the formation of neurospheres. The interaction between MMSCs and neural cells occurred through gap junctions and nanotubes. Our findings expand the understanding of interactions between MMSCs and recipient cells, which allows us to revise the conditions of cellular transplantation therapy for pathological processes in the brain of AD patients.