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• W566965181 abstract "Advances in stem cell biology have challenged the notion that infarcted myocardium isirreparable. The pluripotent ability of stem cells to differentiate into specialized cell lines beganto garner intense interest within cardiology when it was shown in animal models thatintramyocardial injection of bone marrow stem cells (MSCs), or the mobilization of bonemarrow stem cells with spontaneous homing to myocardium, could improve cardiac function andsurvival after induced myocardial infarction (MI) [1, 2]. Furthermore, the existence of stem cellsin myocardium has been identified in animal heart [3, 4], and intense research is under way in anattempt to clarify their potential clinical application for patients with myocardial infarction. Todate, in order to identify the best one, different kinds of stem cells have been studied; these havebeen derived from embryo or adult tissues (i.e. bone marrow, heart, peripheral blood etc.).Currently, three different biologic therapies for cardiovascular diseases are under investigation:cell therapy, gene therapy and the more recent “tissue-engineering” therapy .During my Ph.D. course, first I focalised my study on the isolation and characterization ofCardiac Stem Cells (CSCs) in wild-type and transgenic mice and for this purpose I attended, formore than one year, the Cardiovascular Research Institute of the New York Medical College, inValhalla (NY, USA) under the direction of Doctor Piero Anversa. During this period I learntdifferent Immunohistochemical and Biomolecular techniques, useful for investigating theregenerative potential of stem cells.Then, during the next two years, I studied the new approach of cardiac regenerative medicinebased on “tissue-engineering” in order to investigate a new strategy to regenerate the infractedmyocardium. Tissue-engineering is a promising approach that makes possible the creation ofnew functional tissue to replace lost or failing tissue. This new discipline combines isolatedfunctioning cells and biodegradable 3-dimensional (3D) polymeric scaffolds. The scaffoldtemporarily provides the biomechanical support for the cells until they produce their ownextracellular matrix. Because tissue-engineering constructs contain living cells, they may havethe potential for growth and cellular self-repair and remodeling. In the present study, I examinedwhether the tissue-engineering strategy within hyaluron-based scaffolds would result in theformation of alternative cardiac tissue that could replace the scar and improve cardiac functionafter MI in syngeneic heterotopic rat hearts. Rat hearts were explanted, subjected to left coronarydescending artery occlusion, and then grafted into the abdomen (aorta-aorta anastomosis) ofreceiving syngeneic rat. After 2 weeks, a pouch of 3 mm2 was made in the thickness of theventricular wall at the level of the post-infarction scar. The hyaluronic scaffold, previouslyengineered for 3 weeks with rat MSCs, was introduced into the pouch and the myocardial edgessutured with few stitches. Two weeks later we evaluated the cardiac function by M-Modeechocardiography and the myocardial morphology by microscope analysis.We chose bone marrow-derived mensenchymal stem cells (MSCs) because they have showngreat signaling and regenerative properties when delivered to heart tissue following a myocardialinfarction (MI). However, while the object of cell transplantation is to improve ventricularfunction, cardiac cell transplantation has had limited success because of poor graft viability andlow cell retention, that’s why we decided to combine MSCs with a biopolimeric scaffold.At the end of the experiments we observed that the hyaluronan fibres had not beensubstantially degraded 2 weeks after heart-transplantation. Most MSCs had migrated to thesurrounding infarcted area where they were especially found close to small-sized vessels. Scartissue was moderated in the engrafted region and the thickness of the corresponding ventricularwall was comparable to that of the non-infarcted remote area. Also, the left ventricularshortening fraction, evaluated by M-Mode echocardiography, was found a little bit increasedwhen compared to that measured just before construct transplantation. Therefore, this studysuggests that post-infarction myocardial remodelling can be favourably affected by the graftingof MSCs delivered through a hyaluron-based scaffold" @default.
• W566965181 created "2016-06-24" @default.
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• W566965181 date "2008-06-09" @default.
• W566965181 modified "2023-09-23" @default.
• W566965181 title "Stem Cells as a therapy for myocardial infarction in animal models" @default.
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• W566965181 doi "https://doi.org/10.6092/unibo/amsdottorato/643" @default.
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