Correlation between melanoma angiogenesis and the mesenchymal stem cells and endothelial progenitor cells derived from bone marrow.

Endothelial progenitor cells (EPC) reportedly differentiate into endothelial cells and participate in angiogenesis, including neovascularization at sites of neoplastic development. Recently, we reported that Flk+/CD31-/CD34- mesenchymal stem cells (MSC) possess the potential of differentiating into both endothelial and hematopoietic cells. We hypothesized that these MSC contribute to tumor angiogenesis. This concept is controversial and this study was undertaken to address this controversy. We show that progeny of human MSC as well as differentiated endothelial cells possess the ability to participate in tumor angiogenesis. When human marrow-derived MSC were injected into tail veins of severe combined immunodeficient (SCID) mice engrafted with human malignant melanoma, human cells incorporated into tumor vessels. Moreover, human-derived endothelial cells were identified in the walls of mouse tumor vessels by immunohistology. We report for the first time that similar results are obtained when mice carrying malignant melanoma are injected with differentiated human endothelial cells. Thus, we demonstrate that both differentiated endothelial cells from tissue peripheral to that of a tumor as well as progeny of human MSC have similar capacities to participate in angiogenesis.