EVIDENCE FOR CIRCULATING BONE-MARROW-DERIVED ENDOTHELIAL-CELLS

It has been proposed that hematopoietic and endothelial cells are deri ved from a common cell, the hemangioblast. In this study, we demonstra te that a subset of CD34(+) cells have the capacity to differentiate i nto endothelial cells in vitro in the presence of basic fibroblast gro wth factor, insulin-like growth factor-1, and vascular endothelial gro wth factor. These differentiated endothelial cells are CD34+, stain fo r von Willebrand factor (VWF), and incorporate acetylated low-density lipoprotein (LDL). This suggests the possible existence of a bone marr ow-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 im pervious 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), and tetranucl eotide (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. T hese results strongly suggest that a subset of CD34(+) cells localized in the bone marrow can he mobilized to the peripheral circulation and can colonize endothelial flow surfaces of vascular prostheses. (C) 19 98 by The American Society of Hematology.