Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction

PLoS One. 2012;7(12):e51991. doi: 10.1371/journal.pone.0051991. Epub 2012 Dec 20.

Abstract

Background: To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC) therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with MSC (MSC+hydrogel) could preserve cardiac function and attenuate left ventricular (LV) remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI).

Methodology/principal finding: Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI.

Conclusion/significance: These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Survival
  • Cell Tracking
  • Disease Models, Animal
  • Electrocardiography
  • Female
  • Hydrogel, Polyethylene Glycol Dimethacrylate* / chemistry
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology*
  • Myocardial Infarction / therapy*
  • Myocardium / pathology
  • Rats
  • Time Factors
  • Ventricular Remodeling*

Substances

  • Hydrogel, Polyethylene Glycol Dimethacrylate

Grants and funding

This work was supported by grants from the National Institute for Health and Medical Research and "Fondation de l’Avenir pour la recherche médicale appliquée, ET0 570". Eva Mathieu received a fellowship from the French Ministry of Research and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.