Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction evolution toward heart failure.
OBJECTIVE
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.
Siepe
Matthias
M
Clinic for Cardiovascular Surgery, University Hospital, Freiburg, Germany. matthias.siepe@web.de
Giraud
Marie-Noëlle
MN
Pavlovic
Mladen
M
Receputo
Concetina
C
Beyersdorf
Friedhelm
F
Menasché
Philippe
P
Carrel
Thierry
T
Tevaearai
Hendrik T
HT
D000818:Animals; D000831:Animals, Newborn; D001673:Biodegradation, Environmental; D006339:Heart Rate; D006439:Hemodynamics; D007150:Immunohistochemistry; D032386:Myoblasts, Cardiac; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D013318:Stroke Volume; D023822:Tissue Engineering; D016276:Ventricular Function