title: Prevascularization of cardiac patch on the omentum improves its therapeutic outcome.
abstract: The recent progress made in the bioengineering of cardiac patches offers a new therapeutic modality for regenerating the myocardium after myocardial infarction (MI). We present here a strategy for the engineering of a cardiac patch with mature vasculature by heterotopic transplantation onto the omentum. The patch was constructed by seeding neonatal cardiac cells with a mixture of prosurvival and angiogenic factors into an alginate scaffold capable of factor binding and sustained release. After 48 h in culture, the patch was vascularized for 7 days on the omentum, then explanted and transplanted onto infarcted rat hearts, 7 days after MI induction. When evaluated 28 days later, the vascularized cardiac patch showed structural and electrical integration into host myocardium. Moreover, the vascularized patch induced thicker scars, prevented further dilatation of the chamber and ventricular dysfunction. Thus, our study provides evidence that grafting prevascularized cardiac patch into infarct can improve cardiac function after MI.
authors.affiliation: Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel 84105.
authors.forename: Tal
authors.initials: T
authors.lastname: Dvir
authors.forename: Alon
authors.initials: A
authors.lastname: Kedem
authors.forename: Emil
authors.initials: E
authors.lastname: Ruvinov
authors.forename: Oren
authors.initials: O
authors.lastname: Levy
authors.forename: Inbar
authors.initials: I
authors.lastname: Freeman
authors.forename: Natalie
authors.initials: N
authors.lastname: Landa
authors.forename: Radka
authors.initials: R
authors.lastname: Holbova
authors.forename: Micha S
authors.initials: MS
authors.lastname: Feinberg
authors.forename: Shani
authors.initials: S
authors.lastname: Dror
authors.forename: Yoram
authors.initials: Y
authors.lastname: Etzion
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leor
authors.forename: Smadar
authors.initials: S
authors.lastname: Cohen
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004562:Electrocardiography; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D008297:Male; D008855:Microscopy, Electron, Scanning; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D018919:Neovascularization, Physiologic; D009852:Omentum / Q000098:blood supply* / Q000166:cytology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D016042:Transplantation, Heterotopic; D016896:Treatment Outcome
references.citation: Circulation. 2000 Nov 7;102(19 Suppl 3):III56-61
references.pmid: 11082363
references.citation: Biomaterials. 2009 Apr;30(11):2122-31
references.pmid: 19152972
references.citation: Circulation. 1997 Jul 1;96(1):116-21
references.pmid: 9236425
references.citation: J Biomed Mater Res. 2002 Jun 15;60(4):668-78
references.pmid: 11948526
references.citation: Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1460-9
references.pmid: 18660446
references.citation: FASEB J. 2008 Jun;22(6):1886-93
references.pmid: 18285400
references.citation: Cell Transplant. 2009;18(3):275-82
references.pmid: 19558776
references.citation: Tissue Eng. 2007 Sep;13(9):2185-93
references.pmid: 17518740
references.citation: Eur Surg Res. 1998;30(2):138-43
references.pmid: 9565748
references.citation: Lab Invest. 2001 Apr;81(4):453-63
references.pmid: 11304564
references.citation: Circ Res. 2002 May 31;90(10):1044-54
references.pmid: 12039793
references.citation: Biotechnol Bioeng. 2002 Nov 5;80(3):305-12
references.pmid: 12226863
references.citation: JAMA. 1984 Oct 19;252(15):2034-6
references.pmid: 6207314
references.citation: Cardiovasc Res. 2007 Mar 1;73(4):823-32
references.pmid: 17258698
references.citation: Science. 1997 Feb 14;275(5302):964-7
references.pmid: 9020076
references.citation: Trends Biochem Sci. 2004 Nov;29(11):609-17
references.pmid: 15501680
references.citation: FASEB J. 2007 Oct;21(12):3197-207
references.pmid: 17496162
references.citation: Tissue Eng. 2003 Dec;9(6):1227-32
references.pmid: 14670110
references.citation: Stem Cells. 2008 May;26(5):1376-84
references.pmid: 18308946
references.citation: Circulation. 2002 Dec 10;106(24):3009-17
references.pmid: 12473544
references.citation: Nat Med. 2006 Apr;12(4):452-8
references.pmid: 16582915
references.citation: Tissue Eng. 2005 May-Jun;11(5-6):715-22
references.pmid: 15998213
references.citation: Nat Biotechnol. 2005 Jul;23(7):879-84
references.pmid: 15965465
references.citation: Circulation. 2008 Mar 18;117(11):1388-96
references.pmid: 18316487
references.citation: Nat Biotechnol. 2007 Sep;25(9):1015-24
references.pmid: 17721512
references.citation: J Thorac Cardiovasc Surg. 2004 Jun;127(6):1608-15
references.pmid: 15173714
references.citation: Biomaterials. 2006 Jun;27(17):3249-55
references.pmid: 16490250
references.citation: Annu Rev Physiol. 2006;68:29-49
references.pmid: 16460265
references.citation: Circ Res. 2007 Feb 2;100(2):263-72
references.pmid: 17218605
references.citation: Biomaterials. 2008 Aug;29(22):3260-8
references.pmid: 18462788
references.citation: Circulation. 2005 Aug 30;112(9 Suppl):I173-7
references.pmid: 16159811
references.citation: J Am Coll Cardiol. 2004 Oct 19;44(8):1690-9
references.pmid: 15489105
references.citation: Tissue Eng. 2006 Oct;12(10):2843-52
references.pmid: 17518653
references.citation: Int J Urol. 2006 May;13(5):529-37
references.pmid: 16771721