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- W154328446 abstract "For functional benefits, bone marrow stem cells should engraft and develop functional syncitium with the host myocytes in the infarcted heart. We report that IGF-1 overexpression significantly enhances connexin-43 (Cx-43) in mesenchymal stem cells (MSCs) which promotes their survival and functional integration with host myocardium post-engraftment. IGF-1 gene transduced MSCs ( IGF-1 MSCs) expressed higher IGF-1 ( p < 0.001 ) as compared with GFP gene transduced cells ( GFP MSCs). After 8h anoxia, MSCs, H2C9 and endothelial cells treated with IGF-1 MSCs conditioned medium ( IGF-1 CM) showed higher survival ( p < 0.001 vs GFP MSCs conditioned medium ( GFP CM) supported by higher Akt activation which was abolished by wortmannin. Immunodetection showed Cx-43 plaques in the peripheral areas besides punctate distribution in the cytoplasm around the nucleus in IGF-1 MSCs and IGF-1 CM treated MSCs whereas GFP MSCs and GFP CM treated MSCs showed Cx-43 expression in regions of intimate cell to cell contact only. IGF-1 overexpression or IGF-1 CM treatment of MSCs also induced higher level Akt and p27 activation, and Cx-43 expression as compared with GFP MSCs ( p = 0.02 ) which was abolished by wortmannin. For in vivo studies, 70 μ l DMEM without cells (group-1) or containing 1x10 6 GFP MSC (group-2) or IGF-1 MSC (group-3) were injected intramyocardially in female rat model of coronary artery ligation (n=16/group). The animals were harvested on 7 days and 6 weeks after cell engraftment. FISH and sry -gene analysis on 7 day showed extensive survival of the male donor cells in the heart. Real-time PCR and Western blot on the heart tissue showed higher level of Cx-43 and activation of p27 in group-3 ( p < 0.05 vs group-2). The number of TUNEL + cells was lower in group-3 ( p = 0.01 vs group-2). Immunostaining for α -sarcomeric actin and Cx-43 showed extensive myogenic differentiation of IGF-1 MSCs and gap junction formation between adjacent neofibers. Indices of heart function including ejection fraction (63.05±1.37%) and fractional shortening (28.54±0.92%) were improved in group-3 ( p < 0.001 vs group-2 ) . IGF-1 enhances Cx-43 expression in MSCs and promotes their engraftment and functional integration in the heart and improves heart function." @default.
- W154328446 created "2016-06-24" @default.
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- W154328446 date "2008-10-28" @default.
- W154328446 modified "2023-09-29" @default.
- W154328446 title "Abstract 1416: IGF-1 Gene Transfer Promotes Connexin-43 Expression and Enhances Integration of Bone Marrow Stem Cells in the Infarcted Heart" @default.
- W154328446 doi "https://doi.org/10.1161/circ.118.suppl_18.s_321-c" @default.
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