Binucleated cells generated by nuclear movement during neural transdifferentiation from human bone marrow-derived mesenchymal cells

Abstract

SummaryAlthough it has been reported that bone marrow-derived mesenchymal stromal cells (BM-MSCs) can transdifferentiate into neural cells, the findings are considered unlikely. Cell changes induced by cytotoxicity and cell fusion events are alternative explanations for these observations in culture and transplantation studies, respectively. Here, we showed that BM-MSC neural transdifferentiation involves the formation of dedifferentiated cells which can then redifferentiate into neural-like cells, redifferentiate back to the mesenchymal fate or even repeatedly switch lineages without cell division. Furthermore, we have discovered that nuclei from dedifferentiated cells rapidly move within the cell, adopting different morphologies and even forming binucleated cells. We also noted that dedifferentiated cells position their nucleus at the front of the cell during migration. Our results demonstrated that BM-MSCs can rapidly transdifferentiate into neural-like cells and binucleated BM-MSCs can form with independence of any cell fusion events, suggesting that BM-MSC neural transdifferentiation is a fact, not an artifact.HighlightshBM-MSC neural transdifferentiation involves the formation of dedifferentiated cells.hBM-MSCs could rapidly and repeatedly switch lineages without cell division.Nuclei from hBM-MSCs rapidly move within the cell adopting different morphologies.Binucleated hBM-MSCs can be formed with independence of any cell fusion events.