학술대회 안내 사전등록 안내 초록등록 안내 초록등록/관리 숙박및교통 안내


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COMP-Angiopoietin 1 Enhances the Engraftment of the Mobilized Peripheral Blood Stem Cells to Ischemic Tissue by Induction of Adhesion Molecules
서울대학교 의과대학 내과학교실¹, 서울대학교병원 임상의학연구소 심혈관연구실²,Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology³
이춘수², 김민석¹, 서정원¹, 김태연², 허진², 이해영¹, 강현재¹, 김상현¹, Gou Young Koh³, 김효수¹, 손대원¹, 오병희¹, 박영배¹, 최윤식¹
Background: A major limitation of intracoronary infusion of stem cells is the poor engraftment rate to ischemic tissue(less than 5%). We hypothesized that COMP-Angiopoietin 1 would enhance the adhesion of the mobilized peripheral blood stem cells(PBSCs) to extracellular matrix(ECM) and to endothelial cells (ECs), leading to increased engraftment to ischemic tissue and enhancement of angiogenesis ultimately. Methods and Results: (1)PBSCs mobilized by G-CSF and non-mobilized peripheral blood mononuclear cells(PBMC) were exposed to recombinant human angiopoietin-1(COMP-Ang1) for 3 hours and evaluated the change of their adhesive capacity on mature EC monolayer and on an ECM, fibronectin. COMP-Ang1-stimulated PBSCs showed increased adhesion to ECs and to fibronectin, however no significant changes were observed in PBMCs. (2)COMP-Ang1-stimulated PBSCs expressed more adhesion molecules(ICAM-1, αvβ5, and β2-integrin) in their surface in FACS analysis, whereas no significant changes occurred in PBMCs. (3)The portions of Tie-2+ cells among in PBSCs and in PBMCs were assayed by FACS analysis. Then, to evaluate whether Tie-2 receptor mediated pathway contributes COMP-Ang1-enhanced adhesion of PBSCs, Tie-2 proportion in adherent cells versus in total PBSCs were compared after COMP-Ang1 treatment. The result was that adherent population contained twice as much Tie-2+ cells as total PBSCs(p<0.05). (4)In an athymic hind limb ischemia model, transplantation of the COMP-Ang1-stimulated PBSCs showed improved neovascularization at day 21(perfusion ratio: 0.65±0.09 in COMP-Ang1-treated PBSCs, 0.27±0.12 in control PBSCs, n=8, p<0.05). The engraftment of cells into the ischemic tissue was assessed using CFSE-tagged mobilized PBSCs at day 7. The result showed that significantly more PBSCs were engrafted into vascular structures in COMP-Ang1-stimulated group than in control group(n=8, p<0.05). Conclusion: COMP-Angiopoietin 1 pretreatment increased adhesion molecules of PBSCs, leading to higher efficiency of engraftment rate into ischemic limb. The results of our study suggest that 'priming’ of the mobilized PBSCs with COMP-Ang1 would be a promising strategy enhancing the efficacy of stem cell therapy.


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