title: Cardiac primitive cells become committed to a cardiac fate in adult human heart with chronic ischemic disease but fail to acquire mature phenotype: genetic and phenotypic study.
abstract: Adult human heart hosts a population of cardiac primitive CD117-positive cells (CPCs), which are responsible for physiological tissue homeostasis and regeneration. While the bona fide stem cells express telomerase, their progenies are no longer able to preserve telomeric DNA; hence the balance between their proliferation and differentiation has to be tightly controlled in order to prevent cellular senescence and apoptosis of CPCs before their maturation can be accomplished. We have examined at cellular and molecular level the proliferation, apoptosis and commitment of CPCs isolated from normal (CPC-N) and age-matched pathological adult human hearts (CPC-P) with ischemic heart disease. In the CPC-P, genes related to early stages of developmental processes, nervous system development and neurogenesis, skeletal development, bone and cartilage development were downregulated, while those involved in mesenchymal cell differentiation and heart development were upregulated, together with the transcriptional activation of TGFβ/BMP signaling pathway. In the pathological heart, asymmetric division was the prevalent type of cardiac stem cell division. The population of CPC-P consisted mainly of progenitors of cardiac cell lineages and less precursors; these cells proliferated more, but were also more susceptible to apoptosis with respect to CPC-N. These results indicate that CPCs fail to reach terminal differentiation and functional competence in pathological conditions. Adverse effects of underlying pathology, which disrupts cardiac tissue structure and composition, and cellular senescence, resulting from cardiac stem cell activation in telomere dysfunctional environment, can be responsible for such outcome.
authors.affiliation: Department of Biomorphological and Functional Sciences, University of Naples Federico II, Naples, Italy. dariaanna.nurzynska@unina.it
authors.forename: Daria
authors.initials: D
authors.lastname: Nurzynska
authors.forename: Franca
authors.initials: F
authors.lastname: Di Meglio
authors.forename: Veronica
authors.initials: V
authors.lastname: Romano
authors.forename: Rita
authors.initials: R
authors.lastname: Miraglia
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sacco
authors.forename: Francesca
authors.initials: F
authors.lastname: Latino
authors.forename: Ciro
authors.initials: C
authors.lastname: Bancone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Della Corte
authors.forename: Ciro
authors.initials: C
authors.lastname: Maiello
authors.forename: Cristiano
authors.initials: C
authors.lastname: Amarelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Montagnani
authors.forename: Clotilde
authors.initials: C
authors.lastname: Castaldo
mesh_terms: D000328:Adult; D017209:Apoptosis; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: D053773:Transforming Growth Factor beta1; D019009:Proto-Oncogene Proteins c-kit