| BackgrOundTen millions of patients are sthered from congestive heart failure (CHF) every year inthe world, the cornmonest cause is ischendc heart disease in the deve1oped coUntries, evenin our coUnnySeveral oPtons have been successfully offered in the treatInent of ischemic heart diseaseand consequeDt hean failure, including medical management, heat boplndion,mechhocal circulatory assiStan devices, artificial heart, dynamic cardiomyoplasty as wellas other surgical proceduIes. However, far-ranging myocardial infarCtion and ditheecoronary artery pathOlogicaI changes usually induce sever heart faiIure, wnich is verydifficult to be reversed by above treatInents. Although Heart tranSPlanwhon is the effechvemethod fOr treating end-Stage failing heart, unfortUnately because of the donor shortage,only l5%-20% of the patients can receive heart transplantaion in northem Anerican. In thepast decade, cell tranSplantaion has emerged as a prondsing aPproach for boroving thefailing heart. Even at a same period, angiogenesis has been showed to irnProve cardiacfunction in dithee ischendc myocardium. AIthOugh the definitive mechedsm of heart fallureis edll unclear it is accePtable tha abnormal ventricular remodeling and inadeqUate bloodflow are the major pathological fOundations of the end-stage ischeforc heart failure. ThuS,replacing the fibrosis hssue by imPlaned cells and enhancing the angiogenesis by sustaindpresence of special angiogenic growth factOrs are the tWo attrative aPPraches in thecardiological field.Severai ldllds of ce1ls have been inveshgated as donors fOr wtlantaion in ischemicmyocardium. Now many inveshgators believed that iIIUnatUr and Stem cells are the ideaicell grds for bolantation in the injured myocardiuxn, because forfore cells are morerobUSt than adult cells in ischernic circurnstance. MOreovet, in the native myOcardialcircumtuce, Stem ce1ls can transdifferentiate into cardiomyogenic cells after transPlantaion.Several of growth factors have been investigated fOr genetic revasculariZation in recenthUrnan I trails, and the prelbo results is favorable. However, we thOugh the angiogenicefficacy of angiogenin(ANG) in ischendc myocardium is as good as those, even betterBecause it has been rePort that direct intraInyocardial ANG injection resulted in successaiangiogenesis by our Lab.Therefore, in the current StUdy, we hyPothesized that bosPlantaon of ANG-exPressingautologous bone marrow stromal cells could have beneficial effectS on ischeAncmyocarditnn, by means of increasing angiogenesis in salvaging hOst myocardium andreplacing the necrosis scar with eneded cells.Mdeodsl, BMSCs 1solation, subcultUre and cardiOnyoCyte-the danrentiation.BMSCs were isolated by using gradient centrifugation and prePlatin treatInenrespechvely, then culwtd in IMDM medium with 20% fetal bovine serum. The Purificationand growth velocity of the cells derived from different methods were ndyZed. SeveralWdies againSt CD7l, CD34 and VIII faCtor were used to identify the cell components.MesenchyInai stem cells in BMSCs were incubated with 5-aza tO be induced intocardiomyOgeaic Cels.2, Ad.ANG hection to BMSC8 and re8ult evaluation via anaIy8is of effect of ANGon va8cular endotkflial cell8 promerationBMSCs were Isolated and exPanded using the preplating method. The drichonefficiency and cellular toxicity of adenotris vector to BMSCs wer tested by Ad.LacZinfection procedUr. Ad.ANG exPression in BMSCs and its secretion in cultUre mediumwere measured by haunohistocheInical stahang, western-blot, and ELISA respechvely Toanalyses the biological effect of ANG on cell proliferation, endothelial cells wer inCUatedwith conditionaI medium contalning secreted ANG, and the qUanities of cells wer counted.3, ANG-expressing BMSCs thensplantation into isckemic myocardium, fuuctioualand morPhological 8tUdie842 syngenic Lewis rats (weighing 200g-250g) were used in thes stUdy. ischemic heanfailure was g...
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