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


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.
Davis
Michael E
ME
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Motion
J P Michael
JP
Narmoneva
Daria A
DA
Takahashi
Tomosaburo
T
Hakuno
Daihiko
D
Kamm
Roger D
RD
Zhang
Shuguang
S
Lee
Richard T
RT
D000818:Animals; D001160:Arterioles; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology*; D005782:Gels; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis; D007267:Injections; D007797:Laminin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000637:transplantation; D045333:Nanotubes, Peptide / Q000737:chemistry; D018919:Neovascularization, Physiologic; D011509:Proteoglycans; D012038:Regeneration; D033581:Stem Cell Transplantation
D004338:Drug Combinations; D005782:Gels; D007797:Laminin; D045333:Nanotubes, Peptide; D011509:Proteoglycans; C485184:enhanced green fluorescent protein; C059485:matrigel; D049452:Green Fluorescent Proteins; D003094:Collagen