Abstract 16118: The Presence of the Mother DNA Identifies a Cardiac Stem Cell Class Which Promotes a Remarkable Recovery of the Infarcted Heart
The immortal strand theory defines two categories of human cardiac stem cells (hCSCs), which self-renew by non-random and random segregation of chromatids, respectively. We have employed single cell cloning, nucleotide labeling of newly-synthesized DNA, and distribution of BrdU in anaphase-telophase chromosomes to identify these hCSC subsets. To determine the clinical import of clonal hCSCs with old and new DNA, cells were tagged with EGFP for subsequent tracking. Infarcted immunosuppressed rats were injected with these two categories of hCSCs and their impact on myocardial regeneration and LV function was established 2 weeks later. hCSCs carrying the old DNA resulted in a superior degree of tissue reconstitution; the infarct was replaced completely by growth and differentiation of this category of hCSCs, a reparative response never observed previously. With respect to hCSCs with new DNA, wall thickening, number of myocytes formed, frequency of vascular structures, degree of ongoing myocyte replication, and extent of regenerated mass at this early phase of cardiac repair were 2.2- (p<0.01), 4.9- (p<0.001), 4.4- (p<0.001), 2.6- (p<0.001), and 5.2-fold (p<0.001) higher with hCSCs with the mother DNA. Undifferentiated hCSCs were found in the regenerated myocardium. These cells were isolated, FACS sorted, and injected in a new recipient infarcted heart where they reconstituted the damaged tissue, demonstrating their self-renewal ability following serial transplantation. New myocytes expressed connexin 43, and N-cadherin, and showed sarcomere striation. The human origin of the regenerated myocytes and vascular structures was confirmed by detection of human X-chromosome, Alu sequences and human transcripts by qRT-PCR. Cardiac repair promoted by hCSC classes improved the function of the infarcted heart, but hCSCs with old DNA produced an additional positive effect. The recovery of LV pressures, dP/dt, and diastolic stress was greater than that obtained with hCSCs with new DNA. In conclusion, the impressive recovery in ventricular hemodynamics and anatomy mediated by clonal cells developed from hCSCs carrying the mother DNA underscores the clinical relevance of this stem cell class for the management of ischemic and non-ischemic heart failure.
- © 2011 by American Heart Association, Inc.