Angiogenesis induced by autologous whole bone marrow stem cells transplantation

Background and Objectives: It has been presumed that unknown cells and growth factors in bone marrow might promote angiogenesis, so angiogenesis effect could be enhanced by autologous whole bone marrow (WBM) stem cell transplantation. We compared capillary ratio induced by autologous WBM and bone marrow-mononuclear cells (BM-MNCs) to evaluate the anigiogenic effect of auotologous WBM. In addition, the combined effect of WBM transplantation and granulocyte colony-stimulating factor (G-CSF) injection was examined in an ischemic canine model. Methods and Results: After creating ischemic limb model, autologous WBM and isolated BM-MNCs were transplanted into the ischemic muscle. In other experiments, autologous WBM with recombinant human G-CSF (rhG-CSF) and autologous WBM without rhG-CSF were transplanted into the ischemic muscle. In this study, normal saline was injected into the contralateral sites in each ischemic model as a control group. After 8 weeks of transplantation, angiography and muscle harvest were performed, and then the anigiographic findings and capillary density, as assessed by immunohistochemical staining, were investigated and analyzed. In comparison with the control group, BM-MNCs and WBM transplantation groups showed higher ratios of the capillary density (1.5±0.01 times, p<0.001 and 1.6±0.15 times, p=0.005, respectively). Between the BM-MNCs and WBM transplantation groups, the capillary ratio was 1.2 folds higher in the WBM group than that in the BM-MNCs group, but there was no significantly different (p=0.116). The angiogensis ratios of both the WBM without G-CSF group and the WBM with G-CSF groups were higher (1.6±0.15 times, p=0.004 and 1.8 ±0.01 times, p=0.005, respectively) than that of the control groups. In comparison with the WBM without G-CSF group, the WBM with G-CSF transplantation group revealed a 1.1 folds higher angiogenesis ratio, but there was no statistically significant difference (p=0.095). Conclusions: Autologous WBM transplantation is a simpler method and it is not inferior for inducing therapeutic angiogenesis as compared with isolated BM-MNCs transplantation. In addition to autologous WBM transplantation, intravenous G-CSF injection enhances the angiogenic effect of autologous WBM in an ischemic limb.