Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure

Konrad Urbanek, Daniele Torella, Farooq Sheikh, Antonella De Angelis, Daria Nurzynska, Furio Silvestri, C. Alberto Beltrami, Rossana Bussani, Antonio P. Beltrami, Federico Quaini, Roberto Bolli, Annarosa Leri, Jan Kajstura, Piero Anversa

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerase-competent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased ≈85-fold in acute infarcts and ≈25-fold in chronic infarcts. However, p16INK4a-p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from ≈26,000/cm3 of viable myocardium in acute to ≈7,000/cm3 in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure.

Original languageEnglish (US)
Pages (from-to)8692-8697
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number24
DOIs
StatePublished - Jun 14 2005

Keywords

  • Cardiac progenitor cells
  • Human heart
  • Myocardial infarction

ASJC Scopus subject areas

  • General

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