Viable fibroblast matrix patch induces angiogenesis and increases myocardial blood flow in heart failure after myocardial infarction

Tissue Eng Part A. 2010 Oct;16(10):3065-73. doi: 10.1089/ten.TEA.2009.0589.

Abstract

Background: This study examines a viable biodegradable three-dimensional fibroblast construct (3DFC) in a model of chronic heart failure. The viable fibroblasts, cultured on a vicryl mesh, secrete growth factors that stimulate angiogenesis.

Methods: We ligated the left coronary artery of male Sprague-Dawley rats, implanted the 3DFC 3 weeks after myocardial infarction and obtained end point data 3 weeks later, that is, 6 weeks after myocardial infarction.

Results: Implanting the 3DFC increases (p<0.05) myocardial blood flow twofold, microvessel formation (0.02±0.01 vs. 0.07±0.03 vessels/μm2), and ventricular wall thickness (0.53±0.02 to 1.02±0.17mm). The 3DFC shifts the passive pressure volume loop toward the pressure axis but does not alter left ventricular (LV) ejection fraction, systolic displacement, LV end-diastolic pressure/dimension, or LV cavity area. The 3DFC stimulates selected cytokine activation with a decrease in the proinflammatory cascade and increased total protein content stimulated by strained 3DFC in vitro.

Conclusion: The 3DFC functions as a cell delivery device providing matrix support for resident cell survival and integration into the heart. The imbedded fibroblasts of the 3DFC release a complex blend of cardioactive cytokines promoting increases in microvessel density and anterior wall blood flow but does not improve ejection fraction or alter LV remodeling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Coronary Circulation / physiology
  • Cytokines / metabolism
  • Echocardiography
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism*
  • Heart Failure / therapy*
  • Male
  • Myocardial Infarction / therapy*
  • Neovascularization, Physiologic / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Engineering / methods*

Substances

  • Cytokines