Angiogenesis Induced by the Implantation of Autogenous Whole Bone Marrow Stem Cells in an Ischemic Animal Model

PURPOSE: Bone marrow contains many kinds of primitive cells and endothelial progenitor cells that secrete several growth factors. We hypothesized that angiogenesis could be induced by autogenous whole bone marrow stem cell implantation in an animal ischemic limb. METHOD: A chronic ischemic hind limb model was created by encircling the femoral artery with an ameroid constrictor (2 mm inner diameter) in a dog model. About 20 ml of autogenous whole bone marrow stem cells were aspirated from the femur and then injected into ischemic limb muscles. Contralateral limbs injected with 20 ml of normal saline as controls. To assess angiogenic effects, an angiogram and a histologic evaluation were performed at 8 weeks after bone marrow stem cell implantation. RESULT: Imaging analysis of angiograms showed that newly developed capillaries were significantly more plentiful in treated limbs. Mean capillary density in the treated limb group was significantly greater than that in the control group (151+/-11.7 vs 81.5+/-7.2 cap/mm2, respectively, P<0.05), and the proportion of larger diameter (Fig. 6) newly developed capillaries was significantly higher in treated limbs than in control limbs. CONCLUSION: These findings indicated that autogenous whole bone marrow stem cell implantation increases the efficiency of angiogenesis.

Tissue Engineering of Vascular Graft Using Autogenous Bone Marrow Cell and Allogenous Acellular Vessel

PURPOSE: The objective of this study is to develop a tissue-engineered vascular graft using autologous bone marrow-derived cells (BMCs) and allogenous acellular vascular graft. METHOD: We developed a tissue- engineered vascular patch using autologous BMCs and allogenous acellularized tissue patches. The patches were implanted into the inferior vena cava of a canine in vivo model. Three weeks after implantation, the retrieved patches were investigated by histological and immunohistochemical analyses. RESULT: Cultured BMCs differentiated into endothelium-like and smooth muscle-like cells. The patch graft maintained patent for 3 weeks without any signs of thrombus formation. Histological, immunohistochemical, and scanning electron microscopic analyses of the retrieved patches revealed that new vascular tissues were successfully reconstructed within the patch matrices. CONCLUSION: The tissue-engineered vascular patch using autogenous BMCs and allogenous acellularized matrix maintained patent for 3 weeks and showed vascular tissues generation similar to native blood vessel. The findings of no thrombus and no aneurysmal formation in patch indicated good antithrombogenic property and mechanical property. This study demonstrates the feasibility of utilizing BMCs as an alternative cell source to reconstruct vascular tissues.