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A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix  Takeyoshi.

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Presentation on theme: "A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix  Takeyoshi."— Presentation transcript:

1 A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix  Takeyoshi Ota, MD, PhD, Thomas W. Gilbert, PhD, David Schwartzman, MD, Charles F. McTiernan, PhD, Takashi Kitajima, PhD, Yoshihiro Ito, PhD, Yoshiki Sawa, MD, PhD, Stephen F. Badylak, DVM, MD, PhD, Marco A. Zenati, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 136, Issue 5, Pages (November 2008) DOI: /j.jtcvs Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

2 Figure 1 Intraoperative view after implantation. A, CBD-HGF-UBM patch. B, Dacron patch. C, CBD-HGF-UBM patch 60 days after implantation. The patch is covered with a thin connective tissue with little adhesion. No aneurysm is seen (arrow). D, Dacron patch 60 days after implantation (excised heart). Severe adhesion (already removed) and deformity of the patch are shown (arrow). E, Cross-section of CBD-HGF-UBM patch. The thickness of the patch area approaches that of the normal myocardium. CBD-HGF-UBM, Collagen-binding domain/hepatocyte growth factor/urinary bladder matrix. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

3 Figure 2 In vitro testing. A, HGF determination in preimplant patches. The amount of HGF in the CBD-HGF-UBM patch was significantly higher than that of the rHGF-UBM (∗P < .05). B, Growth of human endothelial cells on UBM discs. CBD-HGF shows significantly greater proliferation potential than HGF in each concentration (∗P < .05). CBD-HGF-UBM, Collagen-binding domain/hepatocyte growth factor/urinary bladder matrix; DW, dry weight; rHGF, recombinant hepatocyte growth factor; The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

4 Figure 3 A, Electrical activity in the patches. CBD-HGF-UBM patch shows the greatest electrical activity compared with the others (∗P < .05). B, LLS of the patch regions. CBD-HGF-UBM patch is positively contractile, whereas the UBM and Dacron patches are dyskinetic (∗P < .05). CBD-HGF-UBM, Collagen-binding domain/hepatocyte growth factor/urinary bladder matrix. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

5 Figure 4 Histologic preparation of the patches 60 days after implantation. A, B, C, CBD-HGF-UBM patches show a monolayer of factor VIII positive cells, and predominantly α-SMA positive cells homogenously spread to the entire patch area beneath the endothelial monolayer. D, E, F, UBM patches show α-SMA positive cells predominantly distributed in the endocardial aspect and the edge of the patch area with an endocardial monolayer of factor VIII-positive cells. G, H, Thickness of α-SMA positive cells is less than that of the CBD-HGF-UBM or UBM patches. Inflammatory reaction was seen along the Dacron patch (arrow). I, CBD-HGF-UBM patch stained with α-sarcomeric actinin stain. Blue, green, and red indicate nuclei, phalloidin, and α-sarcomeric actinin, respectively. A, D, G, Hematoxylin-eosin stain. B, E, H, α-SMA. C, F, Factor VIII. I, α-sarcomeric actinin. Black bar = 200 μm (×100). White bar = 100 μm (×200). Da, Dacron; Epi, epicardial side; CBD-HGF-UBM, collagen-binding domain/hepatocyte growth factor/urinary bladder matrix; H.E., hematoxylin-eosin; SMA, smooth muscle actin. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

6 Figure 5 Capillary density and representative images. Representative factor VIII staining in each patch for capillary density study: A, CBD-HGF-UBM patch. B, UBM patch. C, Dacron patch. Black bar = 100 μm. D, Capillary density. CBD-HGF-UBM patch shows highest capillary density of all (∗P < .05). F, CBD-HGF-UBM patch group. U, UBM patch group, D, Dacron patch group. Da, Dacron patch; CBD-HGF-UBM, collagen-binding domain/hepatocyte growth factor/urinary bladder matrix. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

7 Figure 6 Graphs of quantitative real-time reverse transcription-polymerase chain reaction. CBD-HGF-UBM, Collagen-binding domain/hepatocyte growth factor/urinary bladder matrix; ACTA2, vascular smooth muscle α-actin 2; bFGF, basic fibroblast growth factor; MHC, beta-myosin heavy chain; SM22α, smooth muscle 22α; VEGF, vascular endothelial growth factor; vWF, von Willebrand factor. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © 2008 The American Association for Thoracic Surgery Terms and Conditions

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