Vasculogenesis: A process of vessel formation and its role during Ewing\u27s sarcoma development

Vasculogenesis is the process by which Endothelial Precursor Cells (EPCs) form a vasculature. This process has been traditionally regarded as an embryological process of vessel formation. However, as early as in the 60\u27s the concept of postnatal vasculogenesis was introduced, with a strong resurface of this idea in recent years. Similarly, previous work on a mouse skin tumor model provided us with the grounds to consider the role of vasculogenesis during tumor formation. We examined the contribution of donor bone marrow (BM)-derived cells to neovascularization in recipient nude mice with Ewing\u27s sarcoma. Ewing\u27s sarcoma is a primitive neuroectodermal tumor that most often affects children and young adults between 5 and 30 years of age. Despite multiple attempts to improve the efficacy of chemotherapy for the disease, the 2-year metastases-free survival rate for patients with Ewing\u27s sarcoma has not improved over the past 15 years. New therapeutic approaches are therefore needed to reduce the mortality rate. The contribution of BM endothelial precursor cells in the development of Ewing\u27s sarcoma was examined using different strategies to track the donor-derived cells. Using a BMT model that takes advantage of MHC differences between donor and recipient mice, we have found that donor BM cells were involved in the formation of Ewing\u27s sarcoma vasculature. Cells responsible for this vasculogenesis activity may be located within the stem cell population of the murine BM. These stem cells would not only generate the hematopoietic lineage but they would also generate ECs. Bone marrow SP (Side Population) cells pertain to a subpopulation that can be identified using flow cytometric analysis of Hoechst 33342-stained BM. This population of cells has HSC activity. We have tested the ability of BM SP cells to contribute to vasculogenesis in Ewing\u27s sarcoma using our MHC mismatched transplant model. Mice transplanted with SP cells developed tumor neovessels that were derived from the donor SP cells. Thus, SP cells not only replenished the hematopoietic system of the lethally irradiated mice, but also differentiated into a non-hematopoietic cell lineage and contributed to the formation of the tumor vasculature. In summary, we have demonstrated that BM-derived cells are involved in the generation of the new vasculature during the growth of Ewing\u27s sarcoma. The finding that vasculogenesis plays a role in Ewing\u27s sarcoma development opens the possibility of using genetically modified BM-derived cells for the treatment of Ewing\u27s sarcomas