Mammalian cardiac regeneration after fetal myocardial infarction requires cardiac progenitor cell recruitment

Myron Allukian, Junwang Xu, Michael Morris, Robert Caskey, Wanda Dorsett-Martin, Theodore Plappert, Michael Griswold, Joseph H. Gorman, Robert C. Gorman, Kenneth W. Liechty

Research output: Contribution to journalArticle

Abstract

Background: In contrast to the adult, fetal sheep consistently regenerate functional myocardium after myocardial infarction. We hypothesize that this regeneration is due to the recruitment of cardiac progenitor cells to the infarct by stromal-derived factor-1α (SDF-1α) and that its competitive inhibition will block the regenerative fetal response. Methods: A 20% apical infarct was created in adult and fetal sheep by selective permanent coronary artery ligation. Lentiviral overexpression of mutant SDF-1α competitively inhibited SDF-1α in fetal infarcts. Echocardiography was performed to assess left ventricular function and infarct size. Cardiac progenitor cell recruitment and proliferation was assessed in fetal infarcts at 1 month by immunohistochemistry for nkx2.5 and 5-bromo-2-deoxyuridine. Results: Competitive inhibition of SDF-1α converted the regenerative fetal response into a reparative response, similar to the adult. SDF-inhibited fetal infarcts demonstrated significant infarct expansion by echocardiography (p <0.001) and a significant decrease in the number of nkx2.5+ cells repopulating the infarct (p <0.001). Conclusions: The fetal regenerative response to myocardial infarction requires the recruitment of cardiac progenitor cells and is dependent on SDF1α. This novel model of mammalian cardiac regeneration after myocardial infarction provides a powerful tool to better understand cardiac progenitor cell biology and to develop strategies to cardiac regeneration in the adult.

Original languageEnglish (US)
Pages (from-to)163-170
Number of pages8
JournalAnnals of Thoracic Surgery
Volume96
Issue number1
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Allukian, M., Xu, J., Morris, M., Caskey, R., Dorsett-Martin, W., Plappert, T., ... Liechty, K. W. (2013). Mammalian cardiac regeneration after fetal myocardial infarction requires cardiac progenitor cell recruitment. Annals of Thoracic Surgery, 96(1), 163-170. https://doi.org/10.1016/j.athoracsur.2013.04.005