Bioengineered cardiac grafts: A new approach to repair the infarcted myocardium?

Jonathan Leor, Sharon Aboulafia-Etzion, Ayelet Dar, Lilia Shapiro, Israel M. Barbash, Alexander Battler, Yosef Granot, Smadar Cohen

Research output: Contribution to journalArticlepeer-review

518 Scopus citations

Abstract

Background - The myocardium is unable to regenerate because cardiomyocytes cannot replicate after injury. The heart is therefore an attractive target for tissue engineering to replace infarcted myocardium and enhance cardiac function. We tested the feasibility of bioengineering cardiac tissue within novel 3-dimensional (3D) scaffolds. Methods and Results - We isolated and grew fetal cardiac cells within 3D porous alginate scaffolds. The cell constructs were cultured for 4 days to evaluate viability and morphology before implantation. Light microscopy revealed that within 2 to 3 days in culture, the dissociated cardiac cells form distinctive, multicellular contracting aggregates within the scaffold pores. Seven days after myocardial infarction, rats were randomized to biograft implantation (n=6) or sham-operation (n=6) into the myocardial scar. Echocardiography study was performed before and 65±5 days after implantation to assess left ventricular (LV) remodeling and function. Hearts were harvested 9 weeks after implantation. Visual examination of the biograft revealed intensive neovascularization from the neighboring coronary network. Histological examination revealed the presence of myofibers embedded in collagen fibers and a large number of blood vessels. The specimens showed almost complete disappearance of the scaffold and good integration into the host. Although control animals developed significant LV dilatation accompanied by progressive deterioration in LV contractility, in the biograft-treated rats, attenuation of LV dilatation and no change in LV contractility were observed. Conclusions - Alginate scaffolds provide a conducive environment to facilitate the 3D culturing of cardiac cells. After implantation into the infarcted myocardium, the biografts stimulated intense neovascularization and attenuated LV dilatation and failure in experimental rats compared with controls. This strategy can be used for regeneration and healing of the infarcted myocardium.

Original languageEnglish
Pages (from-to)III56-III61
JournalCirculation
Volume102
Issue number19
DOIs
StatePublished - 7 Nov 2000

Keywords

  • Cells
  • Heart failure
  • Myocardial infarction
  • Myocytes
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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