Bone marrow stem cells can be mobilized by cytokines such as stem cell factor (SCF), granulocyte-colony-stimulating factor (GCSF), or vascular endothelial growth factor (VEGF). These enriched bone marrow cells in the circulation can home to the injured tissues and differentiate, thereby contribute to neovascularization and cardiac repair. In this study, we hypothesize systemic cytokine administration at the time of vascular injury mobilizes these cells to the injured blood vessel. These progenitor cells differentiate into endothelial cells, provide enhanced endothelialization, and inhibit neointimal formation. Sprague-Dawley male rats (body weight 200g) were splenectomized and 2 weeks later were injected s.c. with recombinant human G-CSF, 50 mg/kg/day, once a day for 8 days. At the fifth day, animals were subjected to balloon angioplasty of the carotid artery, and followed by three more days of G-CSF injection. The control animals received injection of normal saline. Animals were killed at varied time points, and carotid arteries were harvested and processed for morphometric analysis, immunochemistry, scan electronic microscopy (SEM) and vascular reactivity measurement. The neointimal formation at 2 weeks after injury was significantly inhibited by 70% in the G-CSF treated animals compared to control. Staining with endothelium specific marker, PECAM-1 shows enhanced endothelialization (>90%) in the G-CSF treated arteries compared to less than 20% in the control. SEM data further confirmed this difference of endothelium coverage between the two groups of animals. The expression of vascular cell adhesion molecule-1 (VCAM-1) was much lower in the G-CSF treated than the control. The effect of G-CSF on restoration of vascular reactivity and proliferation rate of vascular smooth muscle cell were also studied. These findings provide evidence that mobilized bone marrow cells by G-CSF effectively inhibit neointimal formation by homing to the injured site and by facilitating endothelialization, and suggest the possibility of administration of G-CSF as a simple but effective method to prevent neointimal hyperplasia.
Cytokine-mobilized bone marrow cells re-endothealize injured blood vessel and inhibit neointimal formation.
GNECCHI, MASSIMILIANO;
2003-01-01
Abstract
Bone marrow stem cells can be mobilized by cytokines such as stem cell factor (SCF), granulocyte-colony-stimulating factor (GCSF), or vascular endothelial growth factor (VEGF). These enriched bone marrow cells in the circulation can home to the injured tissues and differentiate, thereby contribute to neovascularization and cardiac repair. In this study, we hypothesize systemic cytokine administration at the time of vascular injury mobilizes these cells to the injured blood vessel. These progenitor cells differentiate into endothelial cells, provide enhanced endothelialization, and inhibit neointimal formation. Sprague-Dawley male rats (body weight 200g) were splenectomized and 2 weeks later were injected s.c. with recombinant human G-CSF, 50 mg/kg/day, once a day for 8 days. At the fifth day, animals were subjected to balloon angioplasty of the carotid artery, and followed by three more days of G-CSF injection. The control animals received injection of normal saline. Animals were killed at varied time points, and carotid arteries were harvested and processed for morphometric analysis, immunochemistry, scan electronic microscopy (SEM) and vascular reactivity measurement. The neointimal formation at 2 weeks after injury was significantly inhibited by 70% in the G-CSF treated animals compared to control. Staining with endothelium specific marker, PECAM-1 shows enhanced endothelialization (>90%) in the G-CSF treated arteries compared to less than 20% in the control. SEM data further confirmed this difference of endothelium coverage between the two groups of animals. The expression of vascular cell adhesion molecule-1 (VCAM-1) was much lower in the G-CSF treated than the control. The effect of G-CSF on restoration of vascular reactivity and proliferation rate of vascular smooth muscle cell were also studied. These findings provide evidence that mobilized bone marrow cells by G-CSF effectively inhibit neointimal formation by homing to the injured site and by facilitating endothelialization, and suggest the possibility of administration of G-CSF as a simple but effective method to prevent neointimal hyperplasia.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
