Bone marrow-derived cells are not involved in reendothelialized endothelium as endothelial cells after simple endothelial denudation in mice

Abstract

It has been shown that bone marrow (BM)-derived cells are involved in repaired endothelium induced by a model such as neointima-produced wire injury in mice. This has not been shown in a less invasive model that results in simple reendothelialization. A new wire-induced simple endothelial denudation model of the common carotid artery (CCA) of mice, which did not form neointima at 14 days after the operation, was established. At 7 days after operation, the CCAs were reendothelialized from the aortic arch and the carotid bifurcation but not completely, shown by whole-mount CD31 immunohistochemical staining. Scanning electron microscopy revealed that unendothelialized area was covered with platelets. To determine the involvement of BM-derived cells in the repaired endothelium, the wild-type (WT) C57BL/6 mice, in which BM cells derived from strain-matched green fluorescent protein (GFP)-transgenic mice were transplanted, were operated upon. As a result, there was no GFP-positive endothelial cell (EC) in reendothelialized endothelium, otherwise GFP-positive ‘dendritic’-like cells were recruited under the repaired endothelial layer. Administration of recombinant human erythropoietin [1,000 IU/(kg day) at 0–3 days after operation subcutaneously], which has been shown to increase endothelial progenitor cells in peripheral blood, also could not recruit BM-derived cells as ECs in BM-transplanted mice despite accelerating reendothelialization in WT mice [%reendothelialized area of the administrated group 78.0 ± 9.4% (mean ± SD) vs. the control group 63.0 ± 4.4%, P < 0.05]. These results suggest that BM-derived cells may not be involved in reendothelialization as ECs after simple endothelial denudation in mice.