A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix.
OBJECTIVE
We sought to promote myocardial repair using urinary bladder matrix incorporated with a fusion protein that combined hepatocyte growth factor and fibronectin collagen-binding domain in a porcine model. Collagen-binding domain acted as an intermediary to promote hepatocyte growth factor binding and enhance hepatocyte growth factor stability within urinary bladder matrix.


METHODS
Urinary bladder matrix incorporated with collagen-binding domain and hepatocyte growth factor was implanted into the porcine right ventricular wall (F group) to repair a surgically created defect. Untreated urinary bladder matrix patches (U group) and Dacron patches (D group) served as controls (N = 5/group). Electromechanical mapping was performed 60 days after surgery. Linear local shortening was used to assess regional contractility, and electrical activity was recorded.


RESULTS
Linear local shortening was significantly improved in the F group compared with controls (F: 0.51% +/- 1.57% [P < .05], U: -1.06% +/- 1.84%, D: -2.72% +/- 2.59%), whereas it was inferior to the normal myocardium (13.7% +/- 4.3%; P < .05). Mean electrical activity was 1.49 +/- 0.82 mV in the F group, which was statistically greater than in the control groups (U: 0.93 +/- 0.71 mV; D: 0.30 +/- 0.22 mV; P < .05) and less than the normal myocardium (8.24 +/- 2.49 mV; P < .05). Histologic examination showed predominant alpha-smooth muscle actin positive cells with the F group showing the thickest layer and the D group showing the thinnest layer, with an endocardial endothelial monolayer. Scattered isolated islands of alpha-actinin positive cells were observed only in the F group, but not in the controls, suggesting the presence of cardiomyocytes.


CONCLUSIONS
The collagen-binding domain/hepatocyte growth factor/urinary bladder matrix patch demonstrated increased contractility and electrical activity compared with urinary bladder matrix alone or Dacron and facilitated a homogeneous repopulation of host cells. Urinary bladder matrix incorporated with collagen-binding domain and hepatocyte growth factor may contribute to constructive myocardial remodeling.
Ota
Takeyoshi
T
Division of Cardiac Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Gilbert
Thomas W
TW
Schwartzman
David
D
McTiernan
Charles F
CF
Kitajima
Takashi
T
Ito
Yoshihiro
Y
Sawa
Yoshiki
Y
Badylak
Stephen F
SF
Zenati
Marco A
MA
D000199:Actins / Q000032:analysis; D000818:Animals; D002196:Capillaries / Q000033:anatomy & histology; D003094:Collagen; D055590:Electromagnetic Phenomena; D005109:Extracellular Matrix; D017228:Hepatocyte Growth Factor; D007150:Immunohistochemistry; D009206:Myocardium / Q000166:cytology*; D011093:Polyethylene Terephthalates; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D001743:Urinary Bladder
D000199:Actins; D011093:Polyethylene Terephthalates; D011993:Recombinant Fusion Proteins; D017228:Hepatocyte Growth Factor; D003094:Collagen