Transplantation of cardiac progenitor cell sheet onto infarcted heart promotes cardiogenesis and improves function

Liudmila Zakharova, Diego Mastroeni, Nezahet Mutlu, Michelle Molina, Steven Goldman, Edward Diethrich, Mohamed A. Gaballa

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Aims Cell-based therapy for myocardial infarction (MI) holds great promise; however, the ideal cell type and delivery system have not been established. Obstacles in the field are the massive cell death after direct injection and the small percentage of surviving cells differentiating into cardiomyocytes. To overcome these challenges we designed a novel study to deliver cardiac progenitor cells as a cell sheet. Methods and resultsCell sheets composed of rat or human cardiac progenitor cells (cardiospheres), and cardiac stromal cells were transplanted onto the infarcted myocardium after coronary artery ligation in rats. Three weeks later, transplanted cells survived, proliferated, and differentiated into cardiomyocytes (14.6 ± 4.7). Cell sheet transplantation suppressed cardiac wall thinning and increased capillary density (194 ± 20 vs. 97 ± 24 per mm2, P < 0.05) compared with the untreated MI. Cell migration from the sheet was observed along the necrotic trails within the infarcted area. The migrated cells were located in the vicinity of stromal-derived factor (SDF-1) released from the injured myocardium, and about 20 of these cells expressed CXCR4, suggesting that the SDF-1/CXCR4 axis plays, at least, a role in cell migration. Transplantation of cell sheets resulted in a preservation of cardiac contractile function after MI, as was shown by a greater ejection fraction and lower left ventricular end diastolic pressure compared with untreated MI. Conclusion The scaffold-free cardiosphere-derived cell sheet approach seeks to efficiently deliver cells and increase cell survival. These transplanted cells effectively rescue myocardium function after infarction by promoting not only neovascularization but also inducing a significant level of cardiomyogenesis.

Original languageEnglish (US)
Pages (from-to)40-49
Number of pages10
JournalCardiovascular Research
Volume87
Issue number1
DOIs
StatePublished - Jul 1 2010

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Heart Transplantation
Stem Cells
Myocardial Infarction
Myocardium
Cell Transplantation
Cardiac Myocytes
Cell Movement
Stromal Cells
Cell- and Tissue-Based Therapy
Infarction
Ligation
Cell Survival
Coronary Vessels
Cell Death
Blood Pressure
Injections

Keywords

  • Cardiac progenitor cells
  • Cardiac regeneration
  • Cardiospheres
  • Contractility
  • Myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology
  • Medicine(all)

Cite this

Transplantation of cardiac progenitor cell sheet onto infarcted heart promotes cardiogenesis and improves function. / Zakharova, Liudmila; Mastroeni, Diego; Mutlu, Nezahet; Molina, Michelle; Goldman, Steven; Diethrich, Edward; Gaballa, Mohamed A.

In: Cardiovascular Research, Vol. 87, No. 1, 01.07.2010, p. 40-49.

Research output: Contribution to journalArticle

Zakharova, Liudmila ; Mastroeni, Diego ; Mutlu, Nezahet ; Molina, Michelle ; Goldman, Steven ; Diethrich, Edward ; Gaballa, Mohamed A. / Transplantation of cardiac progenitor cell sheet onto infarcted heart promotes cardiogenesis and improves function. In: Cardiovascular Research. 2010 ; Vol. 87, No. 1. pp. 40-49.
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