Proliferative potential of human kidney endothelial cells: bone marrow-derived cells may not be required for high proliferation

Abstract

Proliferative potential of a single cell, defined as the number of progeny it gives rise to, has been used to define a hierarchy of endothelial progenitor cells in blood. Cells with high proliferative potential are presumed to have greater capacity for endothelium repair. Based on results with commercially available endothelial cells, it has been proposed that a proliferative hierarchy of endothelial cells also exists within blood vessels. It is unknown whether such vessel-derived highly proliferative endothelial cells originate from the bone marrow or whether the supply of precursors is limited to pre-existing cells that reside within vessels. In this study, we isolated normal human renal microvascular endothelial cells (RMEC) and larger cortical vessel endothelial cells (EC) by flow cytometry based on differential expression of human leucocyte antigen (HLA)-DR, and evaluated the proliferative potential of single cells. To determine if highly proliferative clones might derive from bone marrow recruits, HLA-DR expression on RMEC from transplanted kidneys was evaluated using antibodies that distinguish donor cells from recipient cells. We found the proliferative potential of kidney endothelial cells diverse and variable. Subcloning indicated that proliferative potential was determined by epigenetic events. In transplanted kidneys affected with a variety of different injuries, RMEC were donor derived. We conclude that endothelial cells of high proliferative potential exist within human renal blood vessels, even in individuals into their eighth decade of life, and that highly proliferative endothelial cells are unlikely to be bone marrow derived.