improvement of post-infarction cardiac remodeling by grafting stromal stem cells with a...
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Impaired contribution of circulating CD34+ in myocardialischemia-induced neovascularization with ageMohamed Gaballa, Hoang Thai, Steven Goldman. Universityof Arizona, SHC, Tucson, AZ, USA
Impaired angiogenesis is documented in the aged. However,the effects of age on ischemia-induced cardiac vasculogenesisare unknown. To examine changes in ischemia-induced cardiacneovascularization with aging, myocardial infarction (MI) wascreated by LAD ligation in Brown Norway Fisher F344 cross at3 ages: 6 weeks, 6 months, and 24 months rats (n=10 pergroup). A 3D collagen scaffold transplanted onto the heartimmediately after MI and bone marrow derived CD34+ cells or50 ng/kg G-CSF was injected IV. Aging increased MAP, 90±4,115±6, 121±6, n=10, P<0.05, while MI decreased MAP(115±6 to 85±3 and 121±6 to 90±3, n=10, P<0.05) only inthe adult and the aged group and decreased (P<0.05) LVdP/dtin all age groups. All MI groups had higher (P<0.05) LVEDPs.Basal vascular density was decreased (6±0.2 vs. 9±0.4 1/mm2,n=7, P<0.05) with aging. MI increased vascular density in allanimal groups. However the percent of vascular densityincrease after MI is lower (P<0.05) in the old rats. G-CSFadministration after MI had no effect on vascular density. Con-tribution of CD34+ to neovascularization was decreased (27±2,13±2, 8±1 1/mm2, n=5, P<0.05) in both adult and aged. Thenumber of circulating and BM CD34+ cells after MI is de-creased (72±4 vs. 28±4 and 16±1 vs. 12±0.5, n=6, P<0.05) inthe aged. Aging decreased (P<0.05) the levels of secretedVEGF2 (315±40, 213±33, and 81±9 pg/mg, n=6). Thus,myocardial ischemia-induced neovascularization is impaired inthe aged at least in part due to decreased number of circulatingCD34+ and diminished levels of VEGF-2 released by thesecells.
Keywords: Myocardial infarction; Stem cells; Angiogenesis
doi:10.1016/j.yjmcc.2007.03.213
Improvement of post-infarction cardiac remodeling bygrafting stromal stem cells with a hyaluronan-basedscaffoldMarco Carboni, Matvey Tsivian, Giorgio Arpesella,Laura Foroni, Emanuela Fiumana, Gianandrea Pasquinelli,Bruno Nardo, Claudio Caldarera. INRC (I), Italy
Tissue engineering has been proposed as a strategy to rege-nerate the infarcted myocardium. In this study, rat hearts wereexplanted, subjected to left coronary descending artery occlu-sion, and then grafted into the abdomen (aorta–aorta anasto-mosis) of receiving syngeneic rats. After 2 weeks, a pouch of3 mm2 was made in the thickness of the ventricular wall at thelevel of the post-infarction scar. A hyaluronan-benzyl ester non-woven mesh (Hyaff-11®, Fidia Advanced Biopolymers, AbanoTerme, Padua, Italy), previously engineered for 3 weeks with ratbone marrow mesenchymal stem cells (MSCs), was introduced
into the pouch and the myocardial edges sutured with fewstitches. Two weeks later we observed that the hyaluronan fibreshad not been substantially degraded and most MSCs hadmigrated to the surrounding infarcted area where they wereespecially found close to small-sized vessels. Scar tissue wasmoderate in the engrafted region and the thickness of thecorresponding ventricular wall was comparable to that of thenon-infarcted remote area. Also, the left ventricular shorteningfraction, evaluated by M-Mode echography, was not founddecreased when compared to that measured just before con-struct transplantation. Therefore, this study suggests that post-infarction myocardial remodeling can be favourably affected bythe grafting of MSCs delivered through a hyaluronan-basedscaffold.
Acknowledgment
This research was funded by a grant of Compagnia di SanPaolo, Turin, Italy.
Keywords: Cardiac remodeling; Bone marrow stromal cells;Infarction
doi:10.1016/j.yjmcc.2007.03.214
Electrical competence of infarcted heart following stem cellbased regenerative therapy, in a rat modelLeonardo Bocchi, Monia Savi, Roberta Berni, Gallia Graiani,Costanza Lagrasta, Federico Quaini, Ezio Musso. CISTAC,University of Parma, Italy
Electrophysiological consequences of stem cell based car-diac regeneration have not been systematically analysed. Wespecifically addressed this issue in a rat model of myocardialinfarction (MI). In 83 male Wistar rats with 1-month-old MI wemeasured: (i) the incidence of ventricular arrhythmias (VAs) bytelemetry ECG recordings and (ii) basic electrophysiologicalparameters by epicardial mapping. Then, in 43 rats residentcardiac stem cells were mobilized by intramyocardial injectionof IGF-1+HGF while in the remaining 40 control animalssaline was administered. A continuous infusion of BrdU via anosmotic pump was also started. Two weeks later electrophy-siological measurements were repeated and, at sacrifice, leftventricular pressure and ±dP/dt were invasively recorded.Eventually, the heart was perfusion fixed for morphometric andimmunohistochemical studies. Cytochine injection significantlyreduced the incidence of VAs and increased ventricular refrac-toriness and the liminal length for action potential generation.Amelioration of hemodynamics was observed together with apositive remodelling of the left ventricle and a lower volumefraction of fibrosis. BrdU labelling significantly increased inmyocytes of spared as well as infarcted myocardium where wefound clusters of small cycling myocytes expressing Cx43 andN-chaderin. A 2- to 3-fold increased expression of Cx43 in theinfarcted tissue was also shown by Western blot analysis. In
S98 ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S88–S101