Cooperative Effect of Erythropoietin on Angio/Vasculogenesis by Bone Marrow Implantation
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Accession number;05A0202010
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| Title;Cooperative Effect of Erythropoietin on Angio/Vasculogenesis by Bone Marrow Implantation |
| Author;
OZAWA TAKUYA
(Graduate School of Medicine and Dental Sci., Niigata Univ., JPN)
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Journal Title;J Cardiol
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Journal Code:Y0264A
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ISSN:0914-5087
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VOL.45;NO.2;PAGE.88-89(2005)
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| Figure&Table&Reference;FIG.1 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Background. As an application of cell therapy for angio/vasculogenesis, bone marrow implantation (BMI) has been utilized to treat patients with limb and heart ischemia, however, the amplitude of the effect is insufficient. BMI treatment supplies angiogenic precursors as well as angiogenic cytokine-producing cells, especially erythroid cells, into the ischemic loci. Cytokine production by erythroid cells is supposed to be amplified in the presence of erythro-poietin (EPO). We performed in vivo simulation of BMI using murine limb ischemia model and in vitro angiogenesis cultures to demonstrate the overall effect of EPO-assisted BMI and to disclose the cellular and molecular mechanisms, respectively. Methods and Results. Limb-ischemic mice were treated with BMI.+-.EPO, and limb survival, blood flow recovery, and the histology of the ischemic muscle were analyzed. Treatment with BMI+EPO significantly improved limb survival and blood flow. The cumulative effects of EPO on BMI were gain of capillary number and induction of vascular smooth muscle cells. In vitro angiogenesis was also studied. Human peripheral blood-derived erythroid colonies (BFU-e) strongly induced capillary-like structure of human endothelial cells, and the generated capillary networks gathered and grew around the BFU-e. Production of angiogenic factors by human bone marrow cells was analyzed. Erythroid cells, but not non-erythroid cells, in human bone marrow strongly produced vascular endothelial growth factor and placental growth factor. Both the angiogenic effects of BFU-e and angiogenic factor-production by bone marrow erythroid cells were further amplified in the presence of EPO. Conclusions. Simultaneous administration of EPO with BMI strongly enhanced angio/vasculogenesis presumably through production of angiogenic factors as vascular endothelial growth factor and placental growth factor released by erythroid cells are included in implanted bone marrow. (author abst.) |
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