Functional adaptation: the key to plasticity of cardiovascular "stem" cells?

There is increasing evidence that cells of disparate phenotypes displaying various degrees of proliferative capacity engraft and function heterotopically in adult organisms. Efforts were made to reconcile these findings with the embryologic notions of pluripotent stem or progenitor cell, although the nature of the 'stemness' remained elusive. This topic is particularly important for the cardiovascular system, in which cytotrophoblasts, certain tumor cells, monocytes/macrophages, peritoneal mesothelial cells, and others acquire endothelial properties and/or perform endothelial functions. Here we suggest that this pluripotency reflects a fundamental characteristic of cellular diversity, which is manifested as the adaptive response to a functional pressure exerted by the cell's biochemical and biophysical microenvironments that would drive their differentiation. In this model, differentiation is a dynamic, reversible, and open-ended process where the cells would maintain the flexibility to respond to changing environmental clues with a fine tuning of their structure, a property that was previously called cellular plasticity. Pluripotent adult stem cells that display this property in culture, and, perhaps upon in vivo administration, were described. Therefore, we also suggest that differentiation of stem cells is a form of cellular plasticity within the larger context of functional adaptation, whereas their stemness remains associated with self-renewal.