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Therapeutic Benefits of Umbilical Cord Blood-derived Mesenchymal Stem Cells in Ischemic Cardiac Injury
전남대학교병원 심장센터¹ , JB 줄기세포연구소² , 조선대학교병원 산부인과³ , 전남대학교 법의학교실⁴
김용숙¹, 안영근¹ , 홍문화¹ , 박혜정¹ , 권진숙¹ , 이현주² , 송창훈³ , 박종태⁴ , 김계훈¹ , 홍영준¹ , 박형욱¹ , 정명호¹ , 조정관¹ , 박종춘¹
Background: We designed this study to demonstrate the potential of umbilical cord blood (UCB)-mesenchymal stem cells (MSCs) cellular properties. Methods: MSCs were isolated from UCB and characterized. Cell migration was assayed by wound healing assay, and angiogeneic potential of MSC was evaluated by in vitro tube formation. The expression of Ang-1, VEGF isoforms, ie VEGF121, VEGF165, and VEGF189, CARP, and STAT-3 was determined by RT-PCR or Western blot analysis. For in vivo study, myocardial infarction was induced by ligation of LAD for 30 min followed by release in rats, and MSCs were injected around the infarcted area. Before and 2 weeks after surgery, the echocardiograph was performed. Results: The mRNA and protein expression level of CARP in UCB-MSCs were higher than those of BM-MSCs. UCB-MSCs were transfected with CARP siRNA for 72 hours to reduce the CARP protein level to 30% of basal level. In wound healing assay, CARP siRNA transfected UCB-MSCs was delayed than UCB-MSCs. Cell invasion after CARP siRNA transfection were significantly delayed to 1.4-fold compared with control UCB-MSCs (P<0.05). Endothelial growth medium (EGM) was used to trigger the angiogeneic events. Tube formation was triggered by EGM, whereas attenuated by AG490, an inhibitor of STAT3. EGM increased the expression level of Ang-1, VEGF121, VEGF165, and phosphorylation of STAT3. AG490 blocked the tube formation, while resotred by H2O2 (0.2mM). From these data, CARP could be a responsible factor for the cell behavior such as migration and invasion, and STAT3 could be responsible for tube formation of UCB-MSCs. In animal study, Masson's trichrome staining showed fibrosis was decreased in UCB-MSC-treated infarcted myocardium compared with control one. In echocardiograph findings, FS was 43.1%, and EF was 79.3% in UCB-MSC injected rats (control FS; 17.2%, and control EF; 40.6%). Conclusions: Our results demonstrated that UCB-MSCs could contribute to therapeutic application to cardiovascular diseases thanks to their mobility and angiogenetic potentials.


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