Endothelial‐mesenchymal transition as a novel mechanism for tissue regeneration

Abstract

Vascular endothelial cells have shown remarkable plasticity by altering their lineage commitment to generate other cell types to mediate several developmental and pathological processes. We recently found that endothelial cells are converted to a mesenchymal stem cell phenotype through endothelial-mesenchymal transition (EndMT). EndMT has traditionally been implicated in generating the valves and septa of the heart during embryonic development, as well as fibroblast formation in cancer and fibrosis. More recently, we have found that EndMT is a critical mechanism for the formation of endochondral bone during heterotopic ossification, a disabling disorder in which endothelial cells differentiate into chondrocytes and osteocytes through EndMT. Replicating the mechanisms of this disorder may be useful for generating new skeletal tissues for the treatment of degenerative diseases such as osteoarthritis and osteoporosis. Here we describe the EndMT program and discuss the current evidence of EndMT-mediated acquisition of stem cell phenotype and multipotent differentiation capabilities. We suggest that EndMT provides a novel mechanism of using blood vessels to regenerate tissues, rather than traditional stem cell therapies.