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Matthias Siepe
Friedhelm Beyersdorf
Philippe Menasché
Thierry Carrel
Hendrik T. Tevaearai
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Right arrow Cardiac - physiology
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Right arrow Transplantation - heart

J Thorac Cardiovasc Surg 2006;132:124-131
© 2006 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Myoblast-seeded biodegradable scaffolds to prevent post–myocardial infarction evolution toward heart failure

Matthias Siepe, MD a , b , * , Marie-Noëlle Giraud, PhD b , Mladen Pavlovic, MD c , Concetina Receputo a , b , c , d , Friedhelm Beyersdorf, MD, PhD a , Philippe Menasché, MD, PhD d , Thierry Carrel, MD b , Hendrik T. Tevaearai, MD b

a Clinic for Cardiovascular Surgery, University Hospital, Freiburg, Germany
b Clinics for Cardiovascular Surgery, University Hospital, Bern, Switzerland
c Pediatric Cardiology, University Hospital, Bern, Switzerland
d Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Paris, France.

Received for publication November 3, 2005; revisions received January 7, 2006; accepted for publication January 18, 2006.

* Address for reprints: Matthias Siepe, MD, Clinic for Cardiovascular Surgery, University Hospital Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany. (Email: matthias.siepe{at}web.de).

OBJECTIVE(S): Even though the mechanism is not clearly understood, direct intramyocardial cell transplantation has demonstrated potential to treat patients with severe heart failure. We previously reported on the bioengineering of myoblast-based constructs. We investigate here the functional outcome of infarcted hearts treated by implantation of myoblast-seeded scaffolds.

METHODS: Adult Lewis rats with echocardiography-confirmed postinfarction reduced ejection fraction (48.3% ± 1.1%) were randomized to (1) implantation of myoblast-seeded polyurethane patches at the site of infarction (PU-MyoB, n = 11), (2) implantation of nonseeded polyurethane patches (PU, n = 11), (3) sham operation (Sham, n = 12), and (4) direct intramyocardial myoblast injection (MyoB, n = 11). Four weeks later, the functional assessment by echocardiography was repeated, and we additionally performed left ventricular catheterization plus histologic studies.

RESULTS: The ejection fraction significantly decreased in the PU (39.1% ± 2.3%; P = .02) and Sham (39.9% ± 3.5%; P = .04) groups, whereas it remained stable in the PU-MyoB (48.4% ± 3.1%) and MyoB (47.9% ± 3.0%) groups during the observation time. Similarly, left ventricular contractility was significantly higher in groups PU-MyoB (4960 ± 266 mm Hg/s) and MyoB (4748 ± 304 mm Hg/s) than in groups PU (3909 ± 248 mm Hg/s, P = .01) and Sham (4028 ± 199 mm Hg/s, P = .01). Immunohistology identified a high density of myoblasts within the seeded scaffolds without any migration toward the host cardiac tissue and no evidence of cardiac cell differentiation.

CONCLUSIONS: Myoblast-seeded polyurethane scaffolds prevent post–myocardial infarction progression toward heart failure as efficiently as direct intramyocardial injection. The immunohistologic analysis suggests that an indirect mechanism, potentially a paracrine effect, may be assumed.

Abbreviations and Acronyms dP/dtmax = left ventricular contractility; dP/dtmin = left ventricular relaxation; EF = ejection fraction; LVEDP = left ventricular end-diastolic pressure; LVESP = left ventricular end-systolic pressure; LVEDV = left ventricular end-diastolic volume; LVESV = left ventricular end-systolic volume; MI = myocardial infarction; PU = polyurethane; PU-MyoB = myoblast-seeded polyurethane patches at the site of infarction; PU = nonseeded polyurethane patches; MyoB = direct intramyocardial myoblast injection




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