Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells

Circulation. 2005 Feb 1;111(4):442-50. doi: 10.1161/01.CIR.0000153847.47301.80.

Abstract

Background: Promoting survival of transplanted cells or endogenous precursors is an important goal. We hypothesized that a novel approach to promote vascularization would be to create injectable microenvironments within the myocardium that recruit endothelial cells and promote their survival and organization.

Methods and results: In this study we demonstrate that self-assembling peptides can be injected and that the resulting nanofiber microenvironments are readily detectable within the myocardium. Furthermore, the self-assembling peptide nanofiber microenvironments recruit progenitor cells that express endothelial markers, as determined by staining with isolectin and for the endothelial-specific protein platelet-endothelial cell adhesion molecule-1. Vascular smooth muscle cells are recruited to the microenvironment and appear to form functional vascular structures. After the endothelial cell population, cells that express alpha-sarcomeric actin and the transcription factor Nkx2.5 infiltrate the peptide microenvironment. When exogenous donor green fluorescent protein-positive neonatal cardiomyocytes were injected with the self-assembling peptides, transplanted cardiomyocytes in the peptide microenvironment survived and also augmented endogenous cell recruitment.

Conclusions: These experiments demonstrate that self-assembling peptides can create nanofiber microenvironments in the myocardium and that these microenvironments promote vascular cell recruitment. Because these peptide nanofibers may be modified in a variety of ways, this approach may enable injectable tissue regeneration strategies.

Publication types

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

MeSH terms

  • Animals
  • Arterioles
  • Cell Differentiation
  • Cell Movement
  • Cell Survival
  • Collagen
  • Drug Combinations
  • Endothelial Cells / cytology*
  • Gels
  • Genes, Reporter
  • Green Fluorescent Proteins / analysis
  • Injections
  • Laminin
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / cytology*
  • Myocardium / cytology*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / transplantation
  • Nanotubes, Peptide* / chemistry
  • Neovascularization, Physiologic
  • Proteoglycans
  • Regeneration
  • Stem Cell Transplantation*

Substances

  • Drug Combinations
  • Gels
  • Laminin
  • Nanotubes, Peptide
  • Proteoglycans
  • enhanced green fluorescent protein
  • matrigel
  • Green Fluorescent Proteins
  • Collagen