Findings suggest that mesenchymal progenitor cells can support the process of blood vessel formation, which may be relevant during granulation tissue formation at defect sites. The aim of this study was to investigate possible mechanisms of the angiogenic process that can be stimulated by mesenchymal progenitor cells. In the in vivo-like model of the chick embryo chorioallantoic membrane assay, we observed blood vessel ingrowth into collagen sponges containing conditioned medium from undifferentiated bone marrow stromal cells. In the Boyden chamber assay, the conditioned medium was chemotactic for human umbilical vascular endothelial cells and human uterus microvascular endothelial cells, and when cells were placed on Matrigel-coated culture dishes, formation of tubular structures was enhanced. The presence of vascular endothelial growth factor-neutralizing antibodies did not affect the outcome of the two in vitro assays. Bone marrow stromal cell-conditioned medium had no effect on proliferation of endothelial cells, as determined by measuring [3H]thymidine incorporation, and on matrix metalloproteinase 2 expression, as evaluated by reverse transcription-polymerase chain reaction and gelatin zymography. These data indicate that mesenchymal progenitor cells can provide a local environment that supports the ingrowth of blood vessels into a defect site.