Bruno Larrivée1, Peggy L Olive, Aly Karsan. 1. Departments of Medical Biophysics, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Abstract
OBJECTIVE: Recent studies have suggested that endothelial cells derived from circulating endothelial progenitors can be used as carriers for cell-based therapy. However, the in vivo homing properties of mature endothelial cells are still unclear. In this paper, we studied the kinetics and specificity of endothelial homing to sites of angiogenesis. METHODS: The kinetics of the distribution of endothelial cells in mice following intravenous injection of 3H-thymidine-labeled microvascular endothelial cells were examined. To detect the homing of viable and apoptotic endothelial cells, GFP-labeled microvascular endothelial cells were injected intravenously in immunodeficient mice. RESULTS: We observed that endothelial cells injected intravenously transit rapidly through the lungs, but do not home specifically to any organ. We did not observe specific accumulation of endothelial cells in subcutaneously implanted tumors following intravenous injection. Rare GFP-labeled endothelial cells were observed in the proximity of tumor blood vessels. However, similar findings were seen when GFP-labeled apoptotic endothelial cells were injected intravenously. CONCLUSION: These findings suggest that integration of mature endothelial cells to the vasculature is a rare event and that engulfment of apoptotic bodies, independent of nuclear fusion, may be misinterpreted as cell plasticity, and care should be taken in the interpretation of such findings.
OBJECTIVE: Recent studies have suggested that endothelial cells derived from circulating endothelial progenitors can be used as carriers for cell-based therapy. However, the in vivo homing properties of mature endothelial cells are still unclear. In this paper, we studied the kinetics and specificity of endothelial homing to sites of angiogenesis. METHODS: The kinetics of the distribution of endothelial cells in mice following intravenous injection of 3H-thymidine-labeled microvascular endothelial cells were examined. To detect the homing of viable and apoptotic endothelial cells, GFP-labeled microvascular endothelial cells were injected intravenously in immunodeficientmice. RESULTS: We observed that endothelial cells injected intravenously transit rapidly through the lungs, but do not home specifically to any organ. We did not observe specific accumulation of endothelial cells in subcutaneously implanted tumors following intravenous injection. Rare GFP-labeled endothelial cells were observed in the proximity of tumor blood vessels. However, similar findings were seen when GFP-labeled apoptotic endothelial cells were injected intravenously. CONCLUSION: These findings suggest that integration of mature endothelial cells to the vasculature is a rare event and that engulfment of apoptotic bodies, independent of nuclear fusion, may be misinterpreted as cell plasticity, and care should be taken in the interpretation of such findings.