title: Normalization of postinfarct biomechanics using a novel tissue-engineered angiogenic construct.
abstract: BACKGROUND
  Cell-mediated angiogenic therapy for ischemic heart disease has had disappointing results. The lack of clinical translatability may be secondary to cell death and systemic dispersion with cell injection. We propose a novel tissue-engineered therapy, whereby extracellular matrix scaffold seeded with endothelial progenitor cells (EPCs) can overcome these limitations using an environment in which the cells can thrive, enabling an insult-free myocardial cell delivery to normalize myocardial biomechanics.
  
  
  RESULTS
  EPCs were isolated from the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in media or seeded at a density of 5 × 10(6) cells/cm(2) on a collagen/vitronectin matrix. Seeded EPCs underwent ex vivo modification with stromal cell-derived factor-1α (100 ng/mL) to potentiate angiogenic properties and enhance paracrine qualities before construct formation. Scanning electron microscopy and confocal imaging confirmed EPC-matrix adhesion. In vitro vasculogenic potential was assessed by quantifying EPC cell migration and vascular differentiation. There was a marked increase in vasculogenesis in vitro as measured by angiogenesis assay (8 versus 0 vessels/hpf; P=0.004). The construct was then implanted onto ischemic myocardium in a rat model of acute myocardial infarction. Confocal microscopy demonstrated a significant migration of EPCs from the construct to the myocardium, suggesting a direct angiogenic effect. Myocardial biomechanical properties were uniaxially quantified by elastic modulus at 5% to 20% strain. Myocardial elasticity normalized after implant of our tissue-engineered construct (239 kPa versus normal=193, P=0.1; versus infarct=304 kPa, P=0.01).
  
  
  CONCLUSIONS
  We demonstrate restoration and normalization of post-myocardial infarction ventricular biomechanics after therapy with an angiogenic tissue-engineered EPC construct.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Pavan
authors.initials: P
authors.lastname: Atluri
authors.forename: Alen
authors.initials: A
authors.lastname: Trubelja
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Fairman
authors.forename: Philip
authors.initials: P
authors.lastname: Hsiao
authors.forename: John W
authors.initials: JW
authors.lastname: MacArthur
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Cohen
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shudo
authors.forename: John R
authors.initials: JR
authors.lastname: Frederick
authors.forename: Y Joseph
authors.initials: YJ
authors.lastname: Woo
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology* / Q000637:transplantation*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000379:methods*
keywords: extracellular matrix; progenitor cell; revascularization; tissue engineering
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