Sca-1 knockouts mice. In parallel, cardiac non-myocyte cells,previously shown to contain CPCs, were isolated from Sca-1-deficient mice and induced to differentiate into cardiomyo-cytes. The Sca-1-deficient non-myocyte cell populationshowed a reduced capacity to produce differentiated cardio-myocytes in vitro.

All together, these results support a role for Sca-1 and ofSca-1+ cells in maintaining cardiac integrity possibly via theregulation of CPC number and cardiomyocyte differentiation.

Keywords: Stem cells; Cardiac remodeling

doi:10.1016/j.yjmcc.2007.03.218

Skeletal myoblasts and bone marrow cells enhancecontractility of failing cardiomyocytes in co-cultureJoon Lee, Urszula Siedlecka, Mark Stagg, Gopal Soppa,Magdi Yacoub, Cesare Terracciano. Harefield Heart ScienceCentre, NHLI, UK

Cell transplantation has been shown to enhance ventricularfunction in heart failure, but the mechanisms responsible remainunknown. We hypothesized that bone marrow mononuclearcells and skeletal myoblasts cells can influence cardiomyocytesby paracrine mechanisms. Myocardial infarction was induced inadult female Sprague–Dawley rats. Left ventricular ejectionfraction after 3 weeks was 35.5±2.0%. Isolated failing leftventricular myocytes were cultured (density 5.2 cells/mm2) ontheir own (Control) or with either bone marrow mononuclearcells (BM, density 52 cells/mm2) or skeletal myoblasts (SK,density 5.2 cells/mm2). BM and SK were separated from thefailing cardiomyocytes by a Transwell™ porous membrane.After 48 h of co-culture with SK or BM cardiomyocyterelaxation speed was increased. The decay time course of theindo-1 transient was also hastened by SK. SK, but not BM, alsoincreased the cardiomyocyte contraction amplitude compared toControl.

Control BM SK

Sarcomere shortening (nm) 46±6 55±1 91±14*Sarcomere relaxation T50 (ms) 34±6 18±3* 13±2*Indo-1 decay T50 (ms) 22±2 18±2 13±1*

Data represented as mean±SEM, *p<0.05 vs. Control.

We conclude that bone marrow mononuclear cells andskeletal myoblasts enhance cardiomyocyte function in co-culture by paracrine mechanisms, which may help explain thefunctional improvement seen after cell transplantation.

Keywords: Heart failure; Cardiomyocytes; Calcium handling

doi:10.1016/j.yjmcc.2007.03.219

Cardiac stem cells can be generated in damaged heart frombone marrow-derived cellsLucio Barile, Francesco Cerisoli, Roberto Gaetani, ElviraForte, Sergio Ottolenghi, Maria C. Magli, E. Messina. Univ.“La Sapienza” Rome, Italy

There is now strong evidence that the heart harbours cellswith high cardiac muscle regenerative potential. These cells areconsidered to be cardiac stem cells (CSCs). The origin of adultCSC is completely unknown. Although CSCs express Kit, amembrane receptor that marks several stem cell types, includinghematopoietic cells, there is no direct evidence that BM cellscan generate functionally pool of CSCs. To investigate whetherBM cells can contribute to repopulate the cardiac Kit+ CSCspool, we transplanted BM cells from a mouse line expressingtransgenic green fluorescent protein (GFP) under the control ofKit regulatory elements, into wild type irradiated recipients.After hematological reconstitution (4–5 months) and followinga myocardial infarction (MI), cardiac cells were grown in vitroas typical “cardiospheres” (CSs). We next asked whether Kit/GFP+ CSs were functionally capable of regeneration in vivo.We injected 1×105 β-gal labeled CSs-derived cells (CDCs) inthe border zone of three wild type mice, immediately after MI.Fluorescent CSs were obtained from the hearts of transplantedand infarcted mice but not from ones that had not undergoneMI. Many blue stained CDCs could be found engraftedthroughout the infarct region of the mouse heart at 20 days,and a high proportion of them could be identified asdifferentiated cardiomyocytes and vascular cells within viablemyocardium and in scattered islands in the infarct area (but notin the control treated animals). These findings indicate that, atleast in conditions of local CSCs depletion bone marrow cellscan give rise, after homing into the heart, to cells with propertiesof resident Kit+ CSCs.

Keywords: Stem cells; Heart failure; Bone marrow stromal cells

doi:10.1016/j.yjmcc.2007.03.220

Differentiation potential of cardiac stem and progenitorcells in a model of heterotopic heart transplantationT. Zaglia1, S. Bracco1, A. Dedja2, E. Cozzi2, S. Schiaffino1,S. Ausoni1. 1Dept. of Biomedical Sciences, University ofPadua, Italy. 2Dept. Med. and Surg. Sciences, University ofPadua, Italy

Cardiac stem cells were identified in mammalian hearts andthey were found to regenerate cardiomyocytes and vessels wheninjected into an infarcted heart. We used the model ofheterotopic heart transplantation to investigate spontaneouspotential of cardiac stem and progenitor cells to differentiateproperly after tissue damage and remodeling. In a previousstudy, in which hearts from normal rat donors were hetero-topically transplanted into GFP+ transgenic rat hosts, we foundabundant extracardiac GFP+ cells that did not contribute to de

S100 ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S88–S101