Evidence for Circulating Bone Marrow-Derived Endothelial Cells

Abstract

It has been proposed that hematopoietic and endothelial cells are derived from a common cell, the hemangioblast. In this study, we demonstrate that a subset of CD34+ cells have the capacity to differentiate into endothelial cells in vitro in the presence of basic fibroblast growth factor, insulin-like growth factor-1, and vascular endothelial growth factor. These differentiated endothelial cells are CD34+, stain for von Willebrand factor (vWF), and incorporate acetylated low-density lipoprotein (LDL). This suggests the possible existence of a bone marrow-derived precursor endothelial cell. To demonstrate this phenomenon in vivo, we used a canine bone marrow transplantation model, in which the marrow cells from the donor and recipient are genetically distinct. Between 6 to 8 months after transplantation, a Dacron graft, made impervious to prevent capillary ingrowth from the surrounding perigraft tissue, was implanted in the descending thoracic aorta. After 12 weeks, the graft was retrieved, and cells with endothelial morphology were identified by silver nitrate staining. Using the di(CA)n and tetranucleotide (GAAA)n repeat polymorphisms to distinguish between the donor and recipient DNA, we observed that only donor alleles were detected in DNA from positively stained cells on the impervious Dacron graft. These results strongly suggest that a subset of CD34+ cells localized in the bone marrow can be mobilized to the peripheral circulation and can colonize endothelial flow surfaces of vascular prostheses.

Circulating endothelial cells in patients with acute myeloid leukemia

“…Significant CEC elevation has been observed in AML patients diagnosed with WBC >15G/L and an elevated LDH level; factors known to be associated with large tumor mass and poor prognosis. These findings support the concept that CEC detected in cancer patients may be derived from either angiogenic microvessels or from distant uninvolved vessels activated by tumor secreted cytokines or may be mobilized to the peripheral circulation from the bone marrow (5,15). Our results are in agreement with the first observations of Mancuso et al (9) which revealed that rCEC and aCEC are increased in newly diagnosed breast cancer and lymphoma patients and return to healthy controls levels after cure.…”

Prevention of liver fibrosis and liver reconstitution of DMN‐treated rat liver by transplanted EPCs

“…The difference in cell homing between EPCs and RAECs might be explained by different expression levels of CXCR4 by each cell type. Although mature vascular endothelial cells always circulate in peripheral blood, they do not readily incorporate into damaged tissues [37]. Mature endothelial cell transplantation clearly does not affect neovascularization after hind limb ischaemia or myocardial infarction [24,38].…”

Immortalisation of human bone marrow endothelial cells: characterisation of new cell lines

“…To generate these HBMEC cell lines, primary HBMEC were isolated from a bone marrow aspirate. These cells expressed von Willebrand Factor directly after isolation [28], making it unlikely that these cells were circulating CD34 , von Willebrand Factor-negative precursors of endothelial cells [29]. The HBMEC were immortalised by means of the amphotrophic retroviral construct pLXSN16E6/E7.…”