Differentiation, cell fusion, and nuclear fusion during <i>ex vivo</i> repair of epithelium by human adult stem cells from bone marrow stroma

TLDR

The study investigates stem cell differentiation in response to tissue injury. Human mesenchymal stem cells were cocultured with heat‑shocked small airway epithelial cells. A subset of hMSCs differentiated into epithelium‑like cells, restoring the monolayer and expressing normal airway epithelial genes, while up to 1 % fused with epithelial cells to form binucleated cells, some of which also underwent nuclear fusion.

Abstract

To investigate stem cell differentiation in response to tissue injury, human mesenchymal stem cells (hMSCs) were cocultured with heat-shocked small airway epithelial cells. A subset of the hMSCs rapidly differentiated into epithelium-like cells, and they restored the epithelial monolayer. Immunocytochemistry and microarray analyses demonstrated that the cells expressed many genes characteristic of normal small airway epithelial cells. Some hMSCs differentiated directly after incorporation into the epithelial monolayer but other hMSCs fused with epithelial cells. Surprisingly, cell fusion was a frequent rather than rare event, in that up to 1% of the hMSCs added to the coculture system were recovered as binucleated cells expressing an epithelial surface epitope. Some of the fused cells also underwent nuclear fusion.