Recently, the presence of dividing cells was observed in the sections of adult human heart. These cells have been identified as cardiac stem cells, giving rise to the precursors of all cardiac cell lineages, but to the best of our knowledge the isolation of resident stem cells and primitive cells from the adult human heart has not been accomplished before. The aim of our study was the isolation and characterization of primitive cells from adult human heart in the normal and pathological conditions. We used bioptic pieces from normal adult hearts (n=9) and from human hearts explanted due to the ischemic cardiomyopathy (n=12) to obtain the outgrowth of cardiac cells in vitro. The fibroblasts were removed by the depletion during magnetic cell sorting and the primitive cells constituted 10% of the cells in culture. Subsequently, the cells expressing c-kit (CD117) were positively selected by the same method. The progenitor and precursors of all cardiac cell lineages were quantified by immunocytochemistry. Moreover, their apoptosis after induction with H2O2 and proliferation in the normal culture conditions were compared by TdT assay and BrdU incorporation, respectively. While 90% of primitive cells from the normal heart was CD117(+), they constituted only 40% of primitive cells in the pathological hearts. The number of cardiomyocyte progenitors Nkx 2.5(+), α/βMHC(-) among the cells from pathological hearts was 3-fold higher, while the number of precursors CD117(+), α/βMHC(+) did not differ significantly when compared with the cells from normal hearts. Committed to the endothelial cell lineage progenitors Ets-1(+), fVIII(-) and precursors fVIII(+) were 3-fold more abundant in the diseased hearts. The number of smooth muscle cell progenitors GATA6(+), α-SMA(-) and precursors expressing α-SMA did not differ, reflecting their minor role in the cardiac tissue regeneration (smooth muscle cells not being present in the capillaries). The percentage of proliferating CD117(+) cells was 2-fold higher in the pathological hearts, but their level of apoptosis was also 2-fold higher, when compared with the cells from normal hearts. These results suggest that the adult human cardiac primitive cells undergo activation in the chronic pathological conditions and with the augmented progenies generation, they lose the stem cell marker CD117. The increase in the apoptosis rate reflects their increased turnover, which may reduce the number of cells reaching terminal differentiation and allow the progression of heart failure.

Adult human cardiac c-kit positive cells undergo activation in the chronic pathological conditions / Nurzynska, DARIA ANNA; DI MEGLIO, Franca; Castaldo, Clotilde; Arcucci, Alessandro; De Santo, L.; Cotrufo, M.; Montagnani, Stefania. - In: EUROPEAN HEART JOURNAL. - ISSN 0195-668X. - STAMPA. - 27 (Suppl 1):(2006), pp. 552-552.

Adult human cardiac c-kit positive cells undergo activation in the chronic pathological conditions

NURZYNSKA, DARIA ANNA;DI MEGLIO, FRANCA;CASTALDO, CLOTILDE;ARCUCCI, ALESSANDRO;MONTAGNANI, STEFANIA
2006

Abstract

Recently, the presence of dividing cells was observed in the sections of adult human heart. These cells have been identified as cardiac stem cells, giving rise to the precursors of all cardiac cell lineages, but to the best of our knowledge the isolation of resident stem cells and primitive cells from the adult human heart has not been accomplished before. The aim of our study was the isolation and characterization of primitive cells from adult human heart in the normal and pathological conditions. We used bioptic pieces from normal adult hearts (n=9) and from human hearts explanted due to the ischemic cardiomyopathy (n=12) to obtain the outgrowth of cardiac cells in vitro. The fibroblasts were removed by the depletion during magnetic cell sorting and the primitive cells constituted 10% of the cells in culture. Subsequently, the cells expressing c-kit (CD117) were positively selected by the same method. The progenitor and precursors of all cardiac cell lineages were quantified by immunocytochemistry. Moreover, their apoptosis after induction with H2O2 and proliferation in the normal culture conditions were compared by TdT assay and BrdU incorporation, respectively. While 90% of primitive cells from the normal heart was CD117(+), they constituted only 40% of primitive cells in the pathological hearts. The number of cardiomyocyte progenitors Nkx 2.5(+), α/βMHC(-) among the cells from pathological hearts was 3-fold higher, while the number of precursors CD117(+), α/βMHC(+) did not differ significantly when compared with the cells from normal hearts. Committed to the endothelial cell lineage progenitors Ets-1(+), fVIII(-) and precursors fVIII(+) were 3-fold more abundant in the diseased hearts. The number of smooth muscle cell progenitors GATA6(+), α-SMA(-) and precursors expressing α-SMA did not differ, reflecting their minor role in the cardiac tissue regeneration (smooth muscle cells not being present in the capillaries). The percentage of proliferating CD117(+) cells was 2-fold higher in the pathological hearts, but their level of apoptosis was also 2-fold higher, when compared with the cells from normal hearts. These results suggest that the adult human cardiac primitive cells undergo activation in the chronic pathological conditions and with the augmented progenies generation, they lose the stem cell marker CD117. The increase in the apoptosis rate reflects their increased turnover, which may reduce the number of cells reaching terminal differentiation and allow the progression of heart failure.
2006
Adult human cardiac c-kit positive cells undergo activation in the chronic pathological conditions / Nurzynska, DARIA ANNA; DI MEGLIO, Franca; Castaldo, Clotilde; Arcucci, Alessandro; De Santo, L.; Cotrufo, M.; Montagnani, Stefania. - In: EUROPEAN HEART JOURNAL. - ISSN 0195-668X. - STAMPA. - 27 (Suppl 1):(2006), pp. 552-552.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/342977
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