VASCULAR NETWORKS WITHIN THE STROMA OF HUMAN LONG-TERM BONE-MARROW CULTURES

The formation of branching and anastomosing vascular structures has been demonstrated within the stromal layers of human long-term bone marrow cultures (LTBMCs). Such organized vascular structures have not been described previously and may be of functional importance, as adherent granulocyte-predominant haemopoietic foci were more numerous in their interstices and margins than elsewhere in the stromal layers. Mature granulocytes were seen within vascular lumina in a few instances, possibly indicating an attempt to recapitulate the normal process of egress of neutrophils from bone marrow into the circulation. Immunostaining showed that the vascular structures expressed CD31, CD34, and CD105 (endoglin), which were not expressed by stromal fibroblastic cells. Collagen IV and laminin, expressed throughout the stroma, were present in increased amounts where vascular arrays were seen. In contrast, von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1) were expressed equally by the vascular arrays and by stromal fibroblastic cells. Neither the arrays nor the general stroma expressed intercellular adhesion molecule-1 (ICAM-1), ICAM-2, ICAM-3, or endothelial leukocyte adhesion molecule-1 (ELAM-1).