Repair of myocardial infarction by epicardial deposition of bone-marrow-cell-coated muscle patch in a murine model

Ann Thorac Surg. 2004 Oct;78(4):1409-17. doi: 10.1016/j.athoracsur.2003.12.078.

Abstract

Background: Myocardial infarction results in irreversible myocyte loss. In a murine model, we tested the feasibility of a novel repair technique combining bone marrow cell (BMC) transplantation and cardiomyoplasty.

Methods: Myocardial infarction was induced cryogenically in backcrossed ROSA 26 transgenic x C57BL/6J mice (n = 75). Thirty days later, surviving mice (n = 69) were randomized to sham treatment (rethoracotomy only; n = 11), patch only treatment (n = 29), or patch + BMC treatment (n = 29). Abdominal muscle patches were harvested from donor littermates not expressing the beta-galactosidase reporter gene and sutured on the epicardium directly above the infarct zone. Patch only-treated mice received uncoated patches. Patch + BMC-treated mice received patches coated with 5 x 10(6) beta-galactosidase-expressing BMCs embedded in a collagen-rich three-dimensional matrix.

Results: Mortality rate was 52% after muscle patch implantation. Bone marrow cells were able to migrate from muscle patch into the infarct zone, as demonstrated by beta-galactosidase immunostaining, and ultimately constituted 8% of all cells in scar tissue (mean +/- standard deviation, 219 +/- 111/mm2). Angiogenesis and cell survival in the scar were improved by patch + BMC treatment. Left ventricular geometry and cardiac function were improved by patch treatment, with or without BMC, although the effects were stronger after patch + BMC treatment.

Conclusions: Epicardial deposition of a BMC-coated muscle patch is a promising approach to restoring cardiac function after myocardial infarction.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Muscles / transplantation*
  • Animals
  • Bone Marrow Transplantation / methods*
  • Cell Movement
  • Cicatrix / pathology
  • Collagen
  • Crosses, Genetic
  • Feasibility Studies
  • Genes, Reporter
  • Lac Operon
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocardial Infarction / pathology
  • Myocardial Infarction / surgery*
  • Neovascularization, Physiologic
  • Pericardium / surgery*
  • Random Allocation
  • Tissue Engineering*
  • Transplantation, Heterotopic*
  • Wound Healing

Substances

  • Collagen