Microenvironments Inducing IPSCs And BMSCs Into Neuron-like Cells-Reelin's Regulative Role On Cell Differentiation And Polarization

Objective: The present study aims to investigate how the induced pluripotent stem cells(iPSCs) and bone marrow mesenchymal stem cells(BMSCs) differentiate into neuron-like cells under the induction of hippocampal microenvironments and Reelin's regulation.Methods: iPSCs or BMSCs were co-cultured with WT(wild type) organotypic hippocampal slice and cerebral conditioned medium, then the stem cells' differentiation under the induction of hippocampal environment was observed by using fluorescent microscope. In the meantime, stem cells were co-cultured with hippocampal slice and cerebral conditioned medium of reeler(Reelin deletion) mouse respectively, therefore, Reelin's regulation to neuronal differentiation and polarization were understood well.Results: Both adhesive iPSCs and BMSCs on WT hippocampal slice showed lamination of double “C” shape with high density on granular layer and pyramidal layer. The stem cells could differentiate into neuron-like cells with obvious polarization on WT hippocampal slice. For instance, in pyramidal cell layer, the differentiated neuron-like cells were oriented vertically with similar shapes of pyramidal cell in vivo, and the cells within molecule layer were arranged horizontally. In addition, adhesive iPSCs and BMSCs could differentiate into Nestin positive neural stem cells and NeuN positive neurons respectively under WT hippocampal microenvironment. On the other hand, under induction of hippocampal microenvironment of reeler mouse, iPSCs and BMSCs' differentiation could also be seen as in WT mouse, but their lamination was in disorder, and cell polarization were irregular. Moreover, differentiation and polarization of the iPSCs and BMSCs seemed to occur slowly.Conclusion: Both iPSCs and BMSCs can differentiate into neuron-like cells under the induction of hippocampal microenvironments. Reelin is involved in the regulation of neuronal differentiation and cell polarization. Without Reelin, the cellular lamination and polarization appear irregular, and the stem cells' differentiation is delayed.