RATIONALE: According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old template DNA, opposing accumulation of mutations resulting from nonrepaired replication errors and attenuating telomere shortening. OBJECTIVE: Based on the premise of the immortal DNA strand hypothesis, we propose that stem cells retaining the old DNA would represent the most powerful cells for myocardial regeneration. METHODS AND RESULTS: Division of human cardiac stem cells (hCSCs) by nonrandom and random segregation of chromatids was documented by clonal assay of bromodeoxyuridine-tagged hCSCs. Additionally, their growth properties were determined by a series of in vitro and in vivo studies. We report that a small class of hCSCs retain during replication the mother DNA and generate 2 daughter cells, which carry the old and new DNA, respectively. hCSCs with immortal DNA form a pool of nonsenescent cells with longer telomeres and higher proliferative capacity. The self-renewal and long-term repopulating ability of these cells was shown in serial-transplantation assays in the infarcted heart; these cells created a chimeric organ, composed of spared rat and regenerated human cardiomyocytes and coronary vessels, leading to a remarkable restoration of cardiac structure and function. The documentation that hCSCs divide by asymmetrical and symmetrical chromatid segregation supports the view that the human heart is a self-renewing organ regulated by a compartment of resident hCSCs. CONCLUSIONS: The impressive recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs carrying the "mother" DNA underscores the clinical relevance of this stem cell class for the management of heart failure in humans.
RATIONALE: According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old template DNA, opposing accumulation of mutations resulting from nonrepaired replication errors and attenuating telomere shortening. OBJECTIVE: Based on the premise of the immortal DNA strand hypothesis, we propose that stem cells retaining the old DNA would represent the most powerful cells for myocardial regeneration. METHODS AND RESULTS: Division of human cardiac stem cells (hCSCs) by nonrandom and random segregation of chromatids was documented by clonal assay of bromodeoxyuridine-tagged hCSCs. Additionally, their growth properties were determined by a series of in vitro and in vivo studies. We report that a small class of hCSCs retain during replication the mother DNA and generate 2 daughter cells, which carry the old and new DNA, respectively. hCSCs with immortal DNA form a pool of nonsenescent cells with longer telomeres and higher proliferative capacity. The self-renewal and long-term repopulating ability of these cells was shown in serial-transplantation assays in the infarcted heart; these cells created a chimeric organ, composed of spared rat and regenerated human cardiomyocytes and coronary vessels, leading to a remarkable restoration of cardiac structure and function. The documentation that hCSCs divide by asymmetrical and symmetrical chromatid segregation supports the view that the human heart is a self-renewing organ regulated by a compartment of resident hCSCs. CONCLUSIONS: The impressive recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs carrying the "mother" DNA underscores the clinical relevance of this stem cell class for the management of heart failure in humans.
Authors: Claudia Bearzi; Annarosa Leri; Francesco Lo Monaco; Marcello Rota; Arantxa Gonzalez; Toru Hosoda; Martino Pepe; Khaled Qanud; Caroline Ojaimi; Silvana Bardelli; Domenico D'Amario; David A D'Alessandro; Robert E Michler; Stefanie Dimmeler; Andreas M Zeiher; Konrad Urbanek; Thomas H Hintze; Jan Kajstura; Piero Anversa Journal: Proc Natl Acad Sci U S A Date: 2009-08-27 Impact factor: 11.205
Authors: M Elena Padin-Iruegas; Yu Misao; Michael E Davis; Vincent F M Segers; Grazia Esposito; Tomotake Tokunou; Konrad Urbanek; Toru Hosoda; Marcello Rota; Piero Anversa; Annarosa Leri; Richard T Lee; Jan Kajstura Journal: Circulation Date: 2009-08-24 Impact factor: 29.690
Authors: Wilhelm Roell; Thorsten Lewalter; Philipp Sasse; Yvonne N Tallini; Bum-Rak Choi; Martin Breitbach; Robert Doran; Ulrich M Becher; Seong-Min Hwang; Toktam Bostani; Julia von Maltzahn; Andreas Hofmann; Shaun Reining; Britta Eiberger; Bethann Gabris; Alexander Pfeifer; Armin Welz; Klaus Willecke; Guy Salama; Jan W Schrickel; Michael I Kotlikoff; Bernd K Fleischmann Journal: Nature Date: 2007-12-06 Impact factor: 49.962
Authors: Marcello Rota; M Elena Padin-Iruegas; Yu Misao; Antonella De Angelis; Silvia Maestroni; João Ferreira-Martins; Emanuela Fiumana; Raffaella Rastaldo; Michael L Arcarese; Thomas S Mitchell; Alessandro Boni; Roberto Bolli; Konrad Urbanek; Toru Hosoda; Piero Anversa; Annarosa Leri; Jan Kajstura Journal: Circ Res Date: 2008-06-12 Impact factor: 17.367